Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis

Susanne Dittrich, Iris Kühbandner, Stefanie Gehrig, Verena Rickert-Zacharias, Matthew Twigg, Sabine Wege, Cliff Taggart, Felix Herth, Schultz Carsten, Marcus Mall

Research output: Contribution to journalArticle

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Abstract

Neutrophil elastase (NE) is a key risk factor for severity of cystic fibrosis (CF) lung disease. Recent studies identified increased NE activity on the surface of airway neutrophils from CF-like mice and patients with CF. However, the role of surface-bound NE in CF lung disease remains unknown. We determined the relationship between surface-bound NE activity and severity of lung disease in CF.Surface-bound NE activity was measured on sputum neutrophils from 35 CF patients and eight healthy controls using novel lipidated Förster resonance energy transfer reporters and correlated with free NE activity, neutrophil counts, interleukin-8, myeloperoxidase and antiproteases in sputum supernatant, and with lung function parameters.Surface-bound NE activity was increased in CF compared to healthy controls (p<0.01) and correlated with free NE activity (p<0.05) and other inflammation markers (p<0.001). Surface-bound and free NE activity correlated with forced expiratory volume in 1 s % predicted (p<0.01 and p<0.05), but only surface-bound NE activity correlated with plethysmographic functional residual capacity % pred (p<0.01) in patients with CF.We demonstrate that surface-bound NE activity on airway neutrophils correlates with severity of lung disease in patients with CF. Our results suggest that surface-bound NE activity may play an important role in the pathogenesis and serve as novel biomarker in CF lung disease.
LanguageEnglish
Article number1701910
Number of pages11
JournalEuropean Respiratory Journal
Volume51
Issue number3
Publication statusPublished - 29 Mar 2018

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Leukocyte Elastase
Pancreatic Elastase
Sputum
Cystic Fibrosis
Lung Diseases
Neutrophils
Functional Residual Capacity
Energy Transfer
Forced Expiratory Volume
Protease Inhibitors
Interleukin-8
Peroxidase
Biomarkers

Cite this

Dittrich, S., Kühbandner, I., Gehrig, S., Rickert-Zacharias, V., Twigg, M., Wege, S., ... Mall, M. (2018). Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis. European Respiratory Journal, 51(3), [1701910].
Dittrich, Susanne ; Kühbandner, Iris ; Gehrig, Stefanie ; Rickert-Zacharias, Verena ; Twigg, Matthew ; Wege, Sabine ; Taggart, Cliff ; Herth, Felix ; Carsten, Schultz ; Mall, Marcus. / Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis. In: European Respiratory Journal. 2018 ; Vol. 51, No. 3.
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abstract = "Neutrophil elastase (NE) is a key risk factor for severity of cystic fibrosis (CF) lung disease. Recent studies identified increased NE activity on the surface of airway neutrophils from CF-like mice and patients with CF. However, the role of surface-bound NE in CF lung disease remains unknown. We determined the relationship between surface-bound NE activity and severity of lung disease in CF.Surface-bound NE activity was measured on sputum neutrophils from 35 CF patients and eight healthy controls using novel lipidated F{\"o}rster resonance energy transfer reporters and correlated with free NE activity, neutrophil counts, interleukin-8, myeloperoxidase and antiproteases in sputum supernatant, and with lung function parameters.Surface-bound NE activity was increased in CF compared to healthy controls (p<0.01) and correlated with free NE activity (p<0.05) and other inflammation markers (p<0.001). Surface-bound and free NE activity correlated with forced expiratory volume in 1 s {\%} predicted (p<0.01 and p<0.05), but only surface-bound NE activity correlated with plethysmographic functional residual capacity {\%} pred (p<0.01) in patients with CF.We demonstrate that surface-bound NE activity on airway neutrophils correlates with severity of lung disease in patients with CF. Our results suggest that surface-bound NE activity may play an important role in the pathogenesis and serve as novel biomarker in CF lung disease.",
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Dittrich, S, Kühbandner, I, Gehrig, S, Rickert-Zacharias, V, Twigg, M, Wege, S, Taggart, C, Herth, F, Carsten, S & Mall, M 2018, 'Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis', European Respiratory Journal, vol. 51, no. 3, 1701910.

Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis. / Dittrich, Susanne; Kühbandner, Iris; Gehrig, Stefanie; Rickert-Zacharias, Verena; Twigg, Matthew; Wege, Sabine; Taggart, Cliff; Herth, Felix; Carsten, Schultz; Mall, Marcus.

In: European Respiratory Journal, Vol. 51, No. 3, 1701910, 29.03.2018.

Research output: Contribution to journalArticle

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T1 - Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis

AU - Dittrich, Susanne

AU - Kühbandner, Iris

AU - Gehrig, Stefanie

AU - Rickert-Zacharias, Verena

AU - Twigg, Matthew

AU - Wege, Sabine

AU - Taggart, Cliff

AU - Herth, Felix

AU - Carsten, Schultz

AU - Mall, Marcus

N1 - This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication. The journal was chosen due to it being one of the top ranking scientific journals for respiratory science in the world with and impact factor of 12.2.

PY - 2018/3/29

Y1 - 2018/3/29

N2 - Neutrophil elastase (NE) is a key risk factor for severity of cystic fibrosis (CF) lung disease. Recent studies identified increased NE activity on the surface of airway neutrophils from CF-like mice and patients with CF. However, the role of surface-bound NE in CF lung disease remains unknown. We determined the relationship between surface-bound NE activity and severity of lung disease in CF.Surface-bound NE activity was measured on sputum neutrophils from 35 CF patients and eight healthy controls using novel lipidated Förster resonance energy transfer reporters and correlated with free NE activity, neutrophil counts, interleukin-8, myeloperoxidase and antiproteases in sputum supernatant, and with lung function parameters.Surface-bound NE activity was increased in CF compared to healthy controls (p<0.01) and correlated with free NE activity (p<0.05) and other inflammation markers (p<0.001). Surface-bound and free NE activity correlated with forced expiratory volume in 1 s % predicted (p<0.01 and p<0.05), but only surface-bound NE activity correlated with plethysmographic functional residual capacity % pred (p<0.01) in patients with CF.We demonstrate that surface-bound NE activity on airway neutrophils correlates with severity of lung disease in patients with CF. Our results suggest that surface-bound NE activity may play an important role in the pathogenesis and serve as novel biomarker in CF lung disease.

AB - Neutrophil elastase (NE) is a key risk factor for severity of cystic fibrosis (CF) lung disease. Recent studies identified increased NE activity on the surface of airway neutrophils from CF-like mice and patients with CF. However, the role of surface-bound NE in CF lung disease remains unknown. We determined the relationship between surface-bound NE activity and severity of lung disease in CF.Surface-bound NE activity was measured on sputum neutrophils from 35 CF patients and eight healthy controls using novel lipidated Förster resonance energy transfer reporters and correlated with free NE activity, neutrophil counts, interleukin-8, myeloperoxidase and antiproteases in sputum supernatant, and with lung function parameters.Surface-bound NE activity was increased in CF compared to healthy controls (p<0.01) and correlated with free NE activity (p<0.05) and other inflammation markers (p<0.001). Surface-bound and free NE activity correlated with forced expiratory volume in 1 s % predicted (p<0.01 and p<0.05), but only surface-bound NE activity correlated with plethysmographic functional residual capacity % pred (p<0.01) in patients with CF.We demonstrate that surface-bound NE activity on airway neutrophils correlates with severity of lung disease in patients with CF. Our results suggest that surface-bound NE activity may play an important role in the pathogenesis and serve as novel biomarker in CF lung disease.

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Dittrich S, Kühbandner I, Gehrig S, Rickert-Zacharias V, Twigg M, Wege S et al. Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis. European Respiratory Journal. 2018 Mar 29;51(3). 1701910.