Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Thulborn, Samantha J, Ceroni, Alessandro, Haldar, Koirobi, Mistry, Vijay, Cane, Jennifer L, Brightling, Christopher E, Barer, Michael R, Bafadhel, Mona
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297347/
https://www.ncbi.nlm.nih.gov/pubmed/32606645
http://dx.doi.org/10.2147/COPD.S247130
_version_ 1783546985336274944
author Thulborn, Samantha J
Ceroni, Alessandro
Haldar, Koirobi
Mistry, Vijay
Cane, Jennifer L
Brightling, Christopher E
Barer, Michael R
Bafadhel, Mona
author_facet Thulborn, Samantha J
Ceroni, Alessandro
Haldar, Koirobi
Mistry, Vijay
Cane, Jennifer L
Brightling, Christopher E
Barer, Michael R
Bafadhel, Mona
author_sort Thulborn, Samantha J
collection PubMed
description 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 9.95x10(2) gene copies (1.26x10(2) to 1.90x10(4)). 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 (FEV(1) r=0.629, p=0.005; FEV(1)%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.
format Online
Article
Text
id pubmed-7297347
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-72973472020-06-29 Detection of Cell-Dissociated Non-Typeable Haemophilus influenzae in the Airways of Patients with Chronic Obstructive Pulmonary Disease Thulborn, Samantha J Ceroni, Alessandro Haldar, Koirobi Mistry, Vijay Cane, Jennifer L Brightling, Christopher E Barer, Michael R Bafadhel, Mona Int J Chron Obstruct Pulmon Dis Original Research 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 9.95x10(2) gene copies (1.26x10(2) to 1.90x10(4)). 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 (FEV(1) r=0.629, p=0.005; FEV(1)%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. Dove 2020-06-12 /pmc/articles/PMC7297347/ /pubmed/32606645 http://dx.doi.org/10.2147/COPD.S247130 Text en © 2020 Thulborn et al. http://creativecommons.org/licenses/by-nc/3.0/ 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 (http://creativecommons.org/licenses/by-nc/3.0/). 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 (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Thulborn, Samantha J
Ceroni, Alessandro
Haldar, Koirobi
Mistry, Vijay
Cane, Jennifer L
Brightling, Christopher E
Barer, Michael R
Bafadhel, Mona
Detection of Cell-Dissociated Non-Typeable Haemophilus influenzae in the Airways of Patients with Chronic Obstructive Pulmonary Disease
title Detection of Cell-Dissociated Non-Typeable Haemophilus influenzae in the Airways of Patients with Chronic Obstructive Pulmonary Disease
title_full Detection of Cell-Dissociated Non-Typeable Haemophilus influenzae in the Airways of Patients with Chronic Obstructive Pulmonary Disease
title_fullStr Detection of Cell-Dissociated Non-Typeable Haemophilus influenzae in the Airways of Patients with Chronic Obstructive Pulmonary Disease
title_full_unstemmed Detection of Cell-Dissociated Non-Typeable Haemophilus influenzae in the Airways of Patients with Chronic Obstructive Pulmonary Disease
title_short Detection of Cell-Dissociated Non-Typeable Haemophilus influenzae in the Airways of Patients with Chronic Obstructive Pulmonary Disease
title_sort detection of cell-dissociated non-typeable haemophilus influenzae in the airways of patients with chronic obstructive pulmonary disease
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297347/
https://www.ncbi.nlm.nih.gov/pubmed/32606645
http://dx.doi.org/10.2147/COPD.S247130
work_keys_str_mv AT thulbornsamanthaj detectionofcelldissociatednontypeablehaemophilusinfluenzaeintheairwaysofpatientswithchronicobstructivepulmonarydisease
AT ceronialessandro detectionofcelldissociatednontypeablehaemophilusinfluenzaeintheairwaysofpatientswithchronicobstructivepulmonarydisease
AT haldarkoirobi detectionofcelldissociatednontypeablehaemophilusinfluenzaeintheairwaysofpatientswithchronicobstructivepulmonarydisease
AT mistryvijay detectionofcelldissociatednontypeablehaemophilusinfluenzaeintheairwaysofpatientswithchronicobstructivepulmonarydisease
AT canejenniferl detectionofcelldissociatednontypeablehaemophilusinfluenzaeintheairwaysofpatientswithchronicobstructivepulmonarydisease
AT brightlingchristophere detectionofcelldissociatednontypeablehaemophilusinfluenzaeintheairwaysofpatientswithchronicobstructivepulmonarydisease
AT barermichaelr detectionofcelldissociatednontypeablehaemophilusinfluenzaeintheairwaysofpatientswithchronicobstructivepulmonarydisease
AT bafadhelmona detectionofcelldissociatednontypeablehaemophilusinfluenzaeintheairwaysofpatientswithchronicobstructivepulmonarydisease