Back to Journals » International Journal of Chronic Obstructive Pulmonary Disease » Volume 15

Detection of Cell-Dissociated Non-Typeable Haemophilus influenzae in the Airways of Patients with Chronic Obstructive Pulmonary Disease

Authors Thulborn SJ, Ceroni A, Haldar K, Mistry V, Cane JL, Brightling CE, Barer MR, Bafadhel M

Received 24 January 2020

Accepted for publication 20 April 2020

Published 12 June 2020 Volume 2020:15 Pages 1357—1365

DOI https://doi.org/10.2147/COPD.S247130

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Richard Russell


Samantha J Thulborn,1,2 Alessandro Ceroni,3 Koirobi Haldar,4 Vijay Mistry,4 Jennifer L Cane,1,2 Christopher E Brightling,4,5 Michael R Barer,4 Mona Bafadhel1

1Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 2Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK; 3Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 4Department of Immunity, Infection and Inflammation, University of Leicester, Leicester, UK; 5Institute for Lung Health, University of Leicester, Leicester, UK

Correspondence: Mona Bafadhel
Respiratory Medicine Unit, NDM Research Building, Old Campus Road, University of Oxford, Oxford OX3 7FZ, UK
Tel +44 1865 612898
Email mona.bafadhel@ndm.ox.ac.uk

Background: Non-typeable Haemophilus influenzae (NTHi) is the most commonly found pathogen in the lower respiratory airways of patients with COPD. NTHi is predominantly regarded as an intracellular pathogen; however, like most pathogens, it can exist and co-exist in two broad forms: cell-associated (intracellularly or adhered to cells) or cell-dissociated (biofilm dispersed or planktonic). We sought to investigate if cell-dissociated NTHi can be detected from the sputum of COPD patients and assess this relationship to disease severity and airway inflammation.
Methods: DNA was extracted from the sputum plug and cell-free supernatant to quantify absolute (cell-associated and cell-dissociated NTHi) and cell-dissociated NTHi, respectively, from 87 COPD subjects attending an observational longitudinal COPD exacerbation study. NTHi was quantified using TaqMan hydrolysis probes, targeting the OMP P6 gene using qPCR.
Results: At stable state cell-dissociated NTHi was detected 56% of subjects with a median (IQR) of 9.95x102 gene copies (1.26x102 to 1.90x104). Cell-dissociated NTHi correlated with absolute NTHi levels (r=0.34, p< 0.01) but not airway inflammation or spirometry at stable state. At exacerbation, cell-dissociated NTHi correlated with lung function (FEV1 r=0.629, p=0.005; FEV1%predicted r=0.564, p=0.015; FVC r=0.476 p=0.046) and sputum neutrophilic inflammation (% neutrophils r=0.688, p=0.002; total neutrophils r=0.518, p=0.028).
Conclusion: In patients with COPD, NTHi can exist in both cell-associated and cell-dissociated forms. Cell-dissociated NTHi is associated with neutrophilic airway inflammation during exacerbations of COPD and may be a driving factor in worsening lung function during these episodes.

Keywords: NTHi, infection, neutrophils, COPD

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]