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Bronchial epithelial gene expression of NOX isoforms are related to important clinical characteristics in COPD

Richard Russell, Fay Hollins, María Soler Artigas, Anna Esteve-Codino, Gian Andri Thun, Chris Newby, Louise V. Wain, Martin D. Tobin, Simon Heath, Ivo Gut, Deepak Subramanian, Sumit Gupta, David Parr, Dave Singh, Loems Ziegler-Heitbrock, Chris Brightling
European Respiratory Journal 2016 48: PA4012; DOI: 10.1183/13993003.congress-2016.PA4012
Richard Russell
1Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom
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Fay Hollins
1Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom
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María Soler Artigas
2Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, United Kingdom
3Centro Nacional D'Anàlisi Genòmica, Centro Nacional D'Anàlisi Genòmica, Barcelona, Spain
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Anna Esteve-Codino
3Centro Nacional D'Anàlisi Genòmica, Centro Nacional D'Anàlisi Genòmica, Barcelona, Spain
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Gian Andri Thun
3Centro Nacional D'Anàlisi Genòmica, Centro Nacional D'Anàlisi Genòmica, Barcelona, Spain
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Chris Newby
1Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom
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Louise V. Wain
2Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, United Kingdom
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Martin D. Tobin
2Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, United Kingdom
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Simon Heath
3Centro Nacional D'Anàlisi Genòmica, Centro Nacional D'Anàlisi Genòmica, Barcelona, Spain
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Ivo Gut
3Centro Nacional D'Anàlisi Genòmica, Centro Nacional D'Anàlisi Genòmica, Barcelona, Spain
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Deepak Subramanian
4Respiratory Medicine, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
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Sumit Gupta
1Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom
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David Parr
4Respiratory Medicine, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
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Dave Singh
5Medicines Evaluation Unit, University of Manchester, Manchester, United Kingdom
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Loems Ziegler-Heitbrock
6The EvA Study Centre, Comprehensive Pneumology Center, Helmholtz-Zentrum München, Oberschleißheim, Germany
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Chris Brightling
1Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom
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Abstract

Chronic Obstructive Pulmonary Disease (COPD) is characterised by persistent airflow obstruction, airway inflammation and increased oxidative stress. The Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidases (NOX1-5 and DUOX1-2) are implicated in the generation of reactive oxygen species, but their role in COPD is uncertain.

As part of the EvA study bronchial brushings were obtained from 279 COPD subjects and 215 healthy controls. Gene expression of the NOX isoforms was analysed; compared between COPD and health and multiple regression analyses of NOX expression and clinical, physiological, and quantitative (q)CT parameters were performed in COPD cases.

Gene expression of NOX2, 4 and DUOX2 was increased significantly and NOX1 decreased in COPD compared to controls, whereas NOX5 and DUOX1 expression was not different between groups and NOX3 was not present. Multiple regression analyses identified independent associations between: NOX1 and DUOX2 with airflow obstruction (FEV1/FVC ratio) (β=0.006[0.003]; P=0.046 and β=-0.016[0.008]; P=0.035 respectively); NOX1 and NOX2 with airway inflammation (NOX1 with sputum neutrophil and eosinophil % β=0.004[0.002]; P=0.016 and β=-0.056[0.028]; P=0.047 and NOX2 with sputum eosinophils % β=0.004[0.002]; P=0.016); and NOX4 with body mass index (β=0.022[0.005]; P<0.001). NOX isoforms were not independently related to FEV1% predicted or qCT parameters.

In conclusion, NOX1, 2 and 4, and DUOX2 are differentially expressed between COPD and health. Associations between these NOX isoforms and important clinical characteristics suggest a potential role for NOX in the pathogenesis of COPD.

  • COPD - mechanism
  • Functional genomics
  • Inflammation
  • Copyright ©the authors 2016
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Bronchial epithelial gene expression of NOX isoforms are related to important clinical characteristics in COPD
Richard Russell, Fay Hollins, María Soler Artigas, Anna Esteve-Codino, Gian Andri Thun, Chris Newby, Louise V. Wain, Martin D. Tobin, Simon Heath, Ivo Gut, Deepak Subramanian, Sumit Gupta, David Parr, Dave Singh, Loems Ziegler-Heitbrock, Chris Brightling
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4012; DOI: 10.1183/13993003.congress-2016.PA4012

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Bronchial epithelial gene expression of NOX isoforms are related to important clinical characteristics in COPD
Richard Russell, Fay Hollins, María Soler Artigas, Anna Esteve-Codino, Gian Andri Thun, Chris Newby, Louise V. Wain, Martin D. Tobin, Simon Heath, Ivo Gut, Deepak Subramanian, Sumit Gupta, David Parr, Dave Singh, Loems Ziegler-Heitbrock, Chris Brightling
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4012; DOI: 10.1183/13993003.congress-2016.PA4012
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