Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease Patrick Mallia, PhD, Jessica Webber, Simren K.

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Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease Patrick Mallia, PhD, Jessica Webber, Simren K. Gill, PhD, Maria-Belen Trujillo-Torralbo, BSc, Maria Adelaide Calderazzo, MD, Lydia Finney, MD, Eteri Bakhsoliani, MSc, Hugo Farne, MD, Aran Singanayagam, PhD, Joseph Footitt, PhD, Richard Hewitt, MD, Tatiana Kebadze, Julia Aniscenko, Vijay Padmanaban, MPT, Philip L. Molyneaux, PhD, Ian M. Adcock, PhD, Peter J. Barnes, PhD, Kazihuro Ito, PhD, Sarah L. Elkin, PhD, Onn Min Kon, MD, William O. Cookson, PhD, Miriam F. Moffat, PhD, Sebastian L. Johnston, PhD, John S. Tregoning, PhD Journal of Allergy and Clinical Immunology Volume 142, Issue 3, Pages 815-823.e6 (September 2018) DOI: 10.1016/j.jaci.2017.10.017 Copyright © 2017 The Authors Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2018 142, 815-823.e6DOI: (10.1016/j.jaci.2017.10.017) Copyright © 2017 The Authors Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2018 142, 815-823.e6DOI: (10.1016/j.jaci.2017.10.017) Copyright © 2017 The Authors Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2018 142, 815-823.e6DOI: (10.1016/j.jaci.2017.10.017) Copyright © 2017 The Authors Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2018 142, 815-823.e6DOI: (10.1016/j.jaci.2017.10.017) Copyright © 2017 The Authors Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2018 142, 815-823.e6DOI: (10.1016/j.jaci.2017.10.017) Copyright © 2017 The Authors Terms and Conditions

Fig E1 Sputum glucose concentrations according to smoking status in patients with COPD. Journal of Allergy and Clinical Immunology 2018 142, 815-823.e6DOI: (10.1016/j.jaci.2017.10.017) Copyright © 2017 The Authors Terms and Conditions

Fig E2 Sputum glucose concentrations in patients with naturally acquired exacerbations according to exacerbation cause. Journal of Allergy and Clinical Immunology 2018 142, 815-823.e6DOI: (10.1016/j.jaci.2017.10.017) Copyright © 2017 The Authors Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2018 142, 815-823.e6DOI: (10.1016/j.jaci.2017.10.017) Copyright © 2017 The Authors Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2018 142, 815-823.e6DOI: (10.1016/j.jaci.2017.10.017) Copyright © 2017 The Authors Terms and Conditions