Abstract | RATIONALE: 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), FEV1% 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 FEV1 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:
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Authors | James D Chalmers, Kelly L Moffitt, Guillermo Suarez-Cuartin, Oriol Sibila, Simon Finch, Elizabeth Furrie, Alison Dicker, Karolina Wrobel, J Stuart Elborn, Brian Walker, S Lorraine Martin, Sara E Marshall, Jeffrey T-J Huang, Thomas C Fardon |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 195
Issue 10
Pg. 1384-1393
(05 15 2017)
ISSN: 1535-4970 [Electronic] United States |
PMID | 27911604
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Desmosine
- Leukocyte Elastase
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Topics |
- Aged
- Biomarkers
(metabolism)
- Bronchiectasis
(metabolism, physiopathology)
- Cohort Studies
- Desmosine
(metabolism)
- Disease Progression
- Female
- Humans
- Leukocyte Elastase
(metabolism)
- Lung
(metabolism, physiopathology)
- Male
- Middle Aged
- Neutrophils
(metabolism)
- Prospective Studies
- Registries
- Severity of Illness Index
- Sputum
(metabolism)
- United Kingdom
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