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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2020
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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 |
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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 |
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