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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


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

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

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