Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease

Patrick Mallia, Jessica Webber, Simren K Gill, Maria-Belen Trujillo-Torralbo, Maria Adelaide Calderazzo, Lydia Finney, Eteri Bakhsoliani, Hugo Farne, Aran Singanayagam, Joseph Footitt, Richard Hewitt, Tatiana Kebadze, Julia Aniscenko, Vijay Padmanaban, Philip L Molyneaux, Ian M Adcock, Peter J Barnes, Kazihuro Ito, Sarah L Elkin, Onn Min Kon, William O Cookson, Miriam F Moffat, Sebastian L Johnston, John S Tregoning, Patrick Mallia, Jessica Webber, Simren K Gill, Maria-Belen Trujillo-Torralbo, Maria Adelaide Calderazzo, Lydia Finney, Eteri Bakhsoliani, Hugo Farne, Aran Singanayagam, Joseph Footitt, Richard Hewitt, Tatiana Kebadze, Julia Aniscenko, Vijay Padmanaban, Philip L Molyneaux, Ian M Adcock, Peter J Barnes, Kazihuro Ito, Sarah L Elkin, Onn Min Kon, William O Cookson, Miriam F Moffat, Sebastian L Johnston, John S Tregoning

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.

Keywords: Chronic obstructive pulmonary disease; airway inflammation; bacterial infection; glucose; viral infection.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Fig 1
Fig 1
Airway glucose concentrations in stable subjects. All data are shown as medians. A, NL fluid glucose concentrations. B, BAL fluid glucose concentrations. C, Sputum glucose concentrations. D, Sputum glucose concentrations according to GOLD stages. **P < .01 and ***P < .001.
Fig 2
Fig 2
Airway glucose concentrations in patients with COPD exacerbations. All data are shown as medians. A, NL fluid glucose concentrations in subjects experimentally infected with rhinovirus. B, Sputum glucose concentrations in subjects experimentally infected with rhinovirus. C, NL fluid glucose concentrations in patients with naturally acquired COPD exacerbations. D, Sputum glucose concentrations in patients with naturally acquired COPD exacerbations. **P < .01 and ***P < .001, †P < .05 versus nonsmokers, ††P < .01 versus nonsmokers, ‡P < .05 versus baseline, ‡‡P < .01 versus baseline, ‡‡‡P < .001 versus baseline, and #P < .05 versus smokers.
Fig 3
Fig 3
Correlations between sputum glucose concentrations and levels of inflammatory markers in patients with stable COPD. A, Sputum total inflammatory cell numbers. B, Sputum IL-1β levels. C, Sputum IL-8 levels. D, Sputum TNF levels.
Fig 4
Fig 4
Correlations between sputum glucose concentrations and inflammatory markers in patients with naturally acquired COPD exacerbations. A, Sputum total inflammatory cell numbers. B, Sputum IL-1β levels. C, Sputum IL-8 levels. D, Sputum TNF levels.
Fig 5
Fig 5
Correlations between sputum glucose concentrations and viral and bacterial loads. A, Peak sputum viral load in all subjects with experimental rhinovirus infections. B, Peak sputum viral load in patients with COPD and experimental rhinovirus infections. C,In vitro bacterial growth in sputum. D,In vitro bacterial growth in NL fluid. E, Bacterial 16s expression in stable samples. F, Day 15 rhinovirus postinfection bacterial 16s expression.
Fig E1
Fig E1
Sputum glucose concentrations according to smoking status in patients with COPD.
Fig E2
Fig E2
Sputum glucose concentrations in patients with naturally acquired exacerbations according to exacerbation cause.
Fig E3
Fig E3
Sputum glucose concentrations and bacterial species. Gram–ve, Gram negative; H. infl, Haemophilus influenzae; H. para, Haemophilus parainfluenzae; Ps. aer, Pseudomonas aeruginosa; S. aur, Staphylococcus aureus; S. pneum, Streptococcus pneumoniae.
Fig E4
Fig E4
Differential cell counts in patients with naturally acquired exacerbations. A, Percentage of neutrophils in sputum. B, Percentage of macrophages in sputum. C, Percentage of lymphocytes in sputum. D, Percentage of eosinophils in sputum.

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