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Clinical Trial
. 2019 Jul 30;20(1):170.
doi: 10.1186/s12931-019-1145-4.

Neutrophil elastase as a biomarker for bacterial infection in COPD

Samantha J Thulborn  1   2 , Vijay Mistry  3 , Christopher E Brightling  3 , Kelly L Moffitt  4 , David Ribeiro  4 , Mona Bafadhel  5
Affiliations
Clinical Trial

Neutrophil elastase as a biomarker for bacterial infection in COPD

Samantha J Thulborn et al. Respir Res. .

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is predominantly associated with neutrophilic inflammation. Active neutrophil elastase (NE) is a serine proteinase, secreted by neutrophils, in response to inflammation and pathogen invasion. We sought to investigate if NE could be used as a biomarker for bacterial infection in patients with COPD.

Methods: NE was quantified using ProteaseTag® Active NE Immunoassay (ProAxsis, Belfast) from the sputum of COPD subjects at stable state, exacerbation and 2 weeks post treatment visit.

Results: NE was measured in 90 samples from 30 COPD subjects (18 males) with a mean (range) age of 65 (45-81) years and mean (SD) FEV1 of 47% (18). The geometric mean (95%CI) of NE at stable state was 2454 ng/mL (1460 to 4125 ng/mL). There was a significant increase in NE levels at an exacerbation (p = 0.003), and NE levels were higher in a bacterial-associated exacerbation (NE log difference 3.873, 95% CI of log difference 1.396 to 10.740, p = 0.011). NE was an accurate predictor of a bacteria-associated exacerbation (area (95%CI) under the receiver operator characteristic curve 0.812 (0.657 to 0.968).

Conclusion: NE is elevated during exacerbations of COPD. NE may be a viable biomarker for distinguishing a bacterial exacerbation in patients with COPD.

Trial registration: Leicestershire, Northamptonshire and Rutland ethics committee (reference number: 07/H0406/157).

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Conflict of interest statement

All academic authors have completed the ICMJE uniform disclosure form and declare no financial support from, or relationship with any organisation that may have an interest, for the submitted work. MB has received travel support outside the submitted work from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline and consultancy honoraria outside the submitted work from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Pfizer. CEB has received grant support and consultancy honoraria outside the submitted work from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Medimmune, Novartis and Roche. DR and KM are employees of ProAxsis Limited, who manufacture the neutrophil elastase immunoassay used in this work. VM, NA and SJT have no conflicts of interests to declare.

Figures

Fig. 1
Fig. 1
Levels of NE in sputum at stable state and then at an exacerbation in 30 subjects with COPD. Horizontal bars at mean (95% CI) (a). The difference in NE levels from stable to exacerbation state according to GOLD. Mean (95% CI) (b)
Fig. 2
Fig. 2
Levels of sputum NE in subjects with a non-bacterial or bacterial exacerbation (a) and in positive versus negative culture at exacerbations (b). Horizontal bars at mean (95% CI)
Fig. 3
Fig. 3
Levels of NE in sputum across an exacerbation time course in subjects with a non-bacterial associated exacerbation (a) and those with a bacterial exacerbation (b)
See this image and copyright information in PMC

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