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Observational Study
. 2020 Jun 12:15:1357-1365.
doi: 10.2147/COPD.S247130. eCollection 2020.

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

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 Bafadhel  1
Affiliations
Observational Study

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

Samantha J Thulborn et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

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: COPD; NTHi; infection; neutrophils.

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Conflict of interest statement

CEB was funded by a Wellcome Trust Senior Fellowship. MB was funded by a National Institute for Health Research (NIHR) Fellowship. MB has received travel support from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline and consultancy honoraria outside the submitted work from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Pfizer. CEB has received grant support and consultancy honoraria outside the submitted work from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Medimmune, Novartis and Roche. IDP has received grant support and consultancy honoraria outside the submitted work from Aerocrine, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Novartis. The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic interpretation of how bacteria can reside within a host.
Figure 2
Figure 2
Cell-dissociated NTHi levels compared to absolute NTHi levels at stable state. Note: Fifty-nine negative samples not plotted.
Figure 3
Figure 3
Cell-dissociated NTHi levels from stable to exacerbation state. Notes: Data shown as median and interquartile range. Negative values are not displayed.
See this image and copyright information in PMC

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