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      Neutrophil Elastase Activity Is Associated with Exacerbations and Lung Function Decline in Bronchiectasis

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          Abstract

          Rationale: Sputum neutrophil elastase and serum desmosine, which is a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of elastase activity and desmosine with exacerbations and lung function decline in bronchiectasis.

          Methods: This was a single-center prospective cohort study using the TAYBRIDGE (Tayside Bronchiectasis Registry Integrating Datasets, Genomics, and Enrolment into Clinical Trials) registry in Dundee, UK. A total of 433 patients with high-resolution computed tomography–confirmed bronchiectasis provided blood samples for desmosine measurement, and 381 provided sputum for baseline elastase activity measurements using an activity-based immunosassay and fluorometric substrate assay. Candidate biomarkers were tested for their relationship with cross-sectional markers of disease severity, and with future exacerbations, mortality and lung function decline over 3 years.

          Measurement and Main Results: Elastase activity in sputum was associated with the bronchiectasis severity index ( r = 0.49; P < 0.0001) and was also correlated with the Medical Research Council dyspnea score ( r = 0.34; P < 0.0001), FEV 1% predicted ( r = −0.33; P < 0.0001), and the radiological extent of bronchiectasis ( r = 0.29; P < 0.0001). During a 3-year follow-up, elevated sputum elastase activity was associated with a higher frequency of exacerbations ( P < 0.0001) but was not independently associated with mortality. Sputum elastase activity was independently associated with FEV 1 decline (β coefficient, −0.139; P = 0.001). Elastase showed good discrimination for severe exacerbations with an area under the curve of 0.75 (95% confidence interval [CI], 0.72–0.79) and all-cause mortality (area under the curve, 0.70; 95% CI, 0.67–0.73). Sputum elastase activity increased at exacerbations ( P = 0.001) and was responsive to treatment with antibiotics. Desmosine was correlated with sputum elastase ( r = 0.42; P < 0.0001) and was associated with risk of severe exacerbations (hazard ratio 2.7; 95% CI, 1.42–5.29; P = 0.003) but not lung function decline.

          Conclusions: Sputum neutrophil elastase activity is a biomarker of disease severity and future risk in adults with bronchiectasis.

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          Author and article information

          Journal
          Am J Respir Crit Care Med
          Am. J. Respir. Crit. Care Med
          ajrccm
          American Journal of Respiratory and Critical Care Medicine
          American Thoracic Society
          1073-449X
          1535-4970
          15 May 2017
          15 May 2017
          15 May 2017
          15 November 2017
          : 195
          : 10
          : 1384-1393
          Affiliations
          [ 1 ]Scottish Centre for Respiratory Research and
          [ 2 ]School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom
          [ 3 ]Biomolecular Sciences Research Group, School of Pharmacy, and
          [ 6 ]Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences Queen’s University Belfast, Belfast, United Kingdom
          [ 4 ]Respiratory Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; and
          [ 5 ]National Heart and Lung Institute, Imperial College and Royal Brompton Hospital, London, United Kingdom
          Author notes
          Correspondence and requests for reprints should be addressed to James D. Chalmers, M.D., Ph.D., Scottish Centre for Respiratory Research, University of Dundee, Dundee, DD1 9SY, UK. E-mail: jchalmers@ 123456dundee.ac.uk
          [*]

          Joint senior authors.

          Author information
          http://orcid.org/0000-0001-5514-7868
          Article
          PMC5443898 PMC5443898 5443898 201605-1027OC
          10.1164/rccm.201605-1027OC
          5443898
          27911604
          a530aedb-5d3c-493a-a053-1a162c44d709
          Copyright © 2017 by the American Thoracic Society
          History
          : 20 May 2016
          : 01 December 2016
          Page count
          Figures: 6, Tables: 1, Pages: 10
          Categories
          Original Articles
          Pulmonary Infections

          exacerbations,bronchiectasis,neutrophils,inflammation,biomarker

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