Top

Lung

Published in:

Open Access 01-12-2016

Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study

Authors: Arwel Wyn Jones, Richard Robinson, Peer Mohamed, Glen Davison, Hassan Jaysen Izzat, Keir Edward Lewis

Published in: Lung | Issue 6/2016

Abstract

Purpose

The underlying biological mechanisms of the frequent exacerbator phenotype of COPD remain unclear. We compared systemic neutrophil function in COPD patients with or without frequent exacerbations.

Methods

Whole blood from COPD frequent exacerbators (defined as ≥2 moderate–severe exacerbations in the previous 2 years) and non-exacerbators (no exacerbations in the preceding 2 years) was assayed for neutrophil function. Neutrophil function in healthy ex-smoking volunteers was also measured as a control (reference) group.

Results

A total of 52 subjects were included in this study: 26 frequent exacerbators, 18 non-exacerbators and 8 healthy controls. COPD frequent exacerbators had blunted blood neutrophil fMLP-stimulated oxidative burst compared to both non-exacerbators (p < 0.01) and healthy controls (p < 0.001). There were no differences between COPD frequent exacerbators and non-exacerbators in blood neutrophil PMA-stimulated oxidative burst, but both COPD groups had reduced responses compared to healthy controls (p < 0.001). Bacterial-stimulated neutrophil degranulation was greater in frequent exacerbators than non-exacerbators (p < 0.05).

Conclusion

This study is the first to report aberrant receptor-mediated blood neutrophil function in the frequent exacerbator of COPD.

Global initiative for chronic obstructive lung disease. Global strategy for diagnosis, management, and prevention of COPD 2016. http://www.goldcopd.org/. Accessed 28 Jan 2016

Lozano R, Naghavi M, Foreman K et al (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2095–2128CrossRefPubMed

Murray CJ, Lopez AD (2013) Measuring the global burden of disease. N Engl J Med 369:448–457CrossRefPubMed

Celli BR, MacNee W, ATS/ERS committee members (2004) Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 23:932–946CrossRefPubMed

Donaldson GC, Wilkinson TM, Hurst JR et al (2005) Exacerbations and time spent outdoors in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 171:446–452CrossRefPubMed

Seemungal TA, Donaldson GC, Paul EA et al (1998) Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 157:1418–1422CrossRefPubMed

Hurst JR, Vestbo J, Anzueto A et al (2010) Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. New Engl J Med 363:1128–1138CrossRefPubMed

Vestbo J, Agusti A, Wouters EFM et al (2014) Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Should we view chronic obstructive pulmonary disease differently after ECLIPSE? A clinical perspective from the study team. Am J Respir Crit Care Med 189:1022–1030CrossRefPubMed

Berenson CS, Kruzel RL, Eberhardt E et al (2014) Impaired innate immune alveolar macrophage response and the predilection for COPD exacerbations. Thorax 69:811–818CrossRefPubMed

10.

Agusti A, Vestbo J (2011) Current controversies and future perspectives in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 184:507–513CrossRefPubMed

11.

Singh D, Fox SM, Tal-Singer R et al (2014) Altered gene expression in blood and sputum in COPD frequent exacerbators in the ECLIPSE cohort. PLoS ONE 9:e107381CrossRefPubMedPubMedCentral

12.

Sapey E, Stockley RA (2006) COPD exacerbations: aetiology. Thorax 61:250–258CrossRefPubMedPubMedCentral

13.

Stockley JA, Walton GM, Lord JM et al (2013) Aberrant neutrophil functions in stable chronic obstructive pulmonary disease: the neutrophil as an immunotherapeutic target. Int Immunopharmacol 17:1211–1217CrossRefPubMed

14.

Sapey E, Stockley JA, Greenwood H et al (2011) Behavioral and structural differences in migrating peripheral neutrophils from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 183:1176–1186CrossRefPubMed

15.

Wehlin L, Lofdahl M, Lundahl J et al (2005) Reduced intracellular oxygen radical production in whole blood leukocytes from COPD patients and asymptomatic smokers. Chest 128:2051–2058CrossRefPubMed

16.

Yoshikawa T, Dent G, Ward J et al (2007) Impaired neutrophil chemotaxis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175:473–479CrossRefPubMed

17.

Fujimoto K, Yasuo M, Urushibata K et al (2005) Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease. Eur Respir J 25:640–646CrossRefPubMed

18.

Noguera A, Busquets X, Sauleda J et al (1998) Expression of adhesion molecules and G proteins in circulating neutrophils in chronic obstructive pulmonary disease. Am Respir J Crit Care Med 158:1664–1668CrossRef

19.

Oudijk EJ, Nijhuis EH, Zwank MD et al (2005) Systemic inflammation in COPD visualised by gene profiling in peripheral blood neutrophils. Thorax 60:538–544CrossRefPubMedPubMedCentral

20.

Vaitkus M, Lavinskiene S, Barkauskiene D et al (2013) Reactive oxygen species in peripheral blood and sputum neutrophils during bacterial and nonbacterial acute exacerbation of chronic obstructive pulmonary disease. Inflammation 36:1485–1493CrossRefPubMed

21.

Jones AW, Thatcher R, March DS et al (2015) Influence of 4 weeks of bovine colostrum supplementation on neutrophil and mucosal immune responses to prolonged cycling. Scand J Med Sci Sports 25:788–796CrossRefPubMed

22.

Morozov VI, Pryatkin SA, Kalinski MI et al (2003) Effect of exercise to exhaustion on myeloperoxidase and lysozyme release from blood neutrophils. Eur J Appl Physiol 89:257–262CrossRefPubMed

23.

Davison G, Diment BC (2010) Bovine colostrum supplementation attenuates the decrease of salivary lysozyme and enhances the recovery of neutrophil function after prolonged exercise. Br J Nutr 103:1425–1432CrossRefPubMed

24.

Fietta A, Bersani C, De Rose V et al (1988) Evaluation of systemic host defense mechanisms in chronic bronchitis. Respiration 53:37–43CrossRefPubMed

25.

Renkema TE, Postma DS, Noordhoek JA et al (1993) Influence of in vivo prednisolone on increased in vitro O₂-generation by neutrophils in emphysema. Eur Respir J 6:90–95PubMed

26.

Noguera A, Batle S, Miralles C et al (2001) Enhanced neutrophil response in chronic obstructive pulmonary disease. Thorax 56:432–437CrossRefPubMedPubMedCentral

27.

Freitas M, Porto G, Lima JL et al (2008) Isolation and activation of human neutrophils in vitro. The importance of the anticoagulant used during blood collection. Clin Biochem 41:570–575CrossRefPubMed

28.

Kuijpers TW, Tool AT, van der Schoot CE et al (1991) Membrane surface antigen expression on neutrophils: a reappraisal of the use of surface markers for neutrophil activation. Blood 78:1105–1111PubMed

29.

van Eeden SF, Klut ME, Walker BA et al (1999) The use of flow cytometry to measure neutrophil function. J Immunol Methods 232:23–43CrossRefPubMed

30.

Decoursey TE, Ligeti E (2005) Regulation and termination of NADPH oxidase activity. Cell Mol Life Sci 62:2173–2193CrossRefPubMed

31.

Jaillon S, Galdiero MR, Del Prete D et al (2013) Neutrophils in innate and adaptive immunity. Semin Immunopathol 35:377–394CrossRefPubMed

32.

Baines KJ, Simpson JL, Gibson PG (2011) Innate immune responses are increased in chronic obstructive pulmonary disease. PLoS One 6:e18426CrossRefPubMedPubMedCentral

33.

Carter RI, Mumford RA, Treonze KM et al (2011) The fibrinogen cleavage product Aalpha-Val360, a specific marker of neutrophil elastase activity in vivo. Thorax 66:686–691CrossRefPubMed

34.

Carter RI, Ungurs MJ, Mumford RA et al (2013) Aalpha-Val360: a marker of neutrophil elastase and COPD disease activity. Eur Respir J 41:31–38CrossRefPubMed

35.

Aldonyte R, Jansson L, Piitulainen E et al (2003) Circulating monocytes from healthy individuals and COPD patients. Respir Res 4:11CrossRefPubMedPubMedCentral

36.

Vlahos R, Wark PA, Anderson GP et al (2012) Glucocorticosteroids differentially regulate MMP-9 and neutrophil elastase in COPD. PLoS One 7:e33277CrossRefPubMedPubMedCentral

37.

Zhang X, Moilanen E, Kankaanranta H (2001) Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophil apoptosis. Eur J Pharmacol 431:365–371CrossRefPubMed

38.

Koutsokera A, Stolz D, Loukides S et al (2012) Systemic biomarkers in exacerbations of COPD: the evolving clinical challenge. Chest 141:396–405CrossRefPubMed

Title: Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study
Authors: Arwel Wyn Jones
Richard Robinson
Peer Mohamed
Glen Davison
Hassan Jaysen Izzat
Keir Edward Lewis
Publication date: 01-12-2016
Publisher: Springer US
Published in: Lung / Issue 6/2016
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-016-9930-z

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study

Abstract

Purpose

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2016

Ultrasound-Guided Abrams Pleural Biopsy vs CT-Guided Tru-Cut Pleural Biopsy in Malignant Pleural Disease, a 3-Year Follow-up Study

Advances in Imaging and Automated Quantification of Pulmonary Diseases in Non-neoplastic Diseases

The Association Between Bone Mineral Density and Airflow Limitation in a Cohort of Fit Elderly Women

The Effect of Fatigue and Fatigue Intensity on Exercise Tolerance in Moderate COPD

Radial Ultrasound-Assisted Transbronchial Biopsy: A New Diagnostic Approach for Non-Resolving Pulmonary Infiltrates in Neutropenic Hemato-Oncological Patients

Changes in Red Cell Distribution Width During Hospitalization for Community-Acquired Pneumonia: Clinical Characteristics and Prognostic Significance

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page