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

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Teacher spread

0.330 · how far apart the two teachers sit on this one work

Validation status

score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

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

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The record

Venue

American Journal of Respiratory and Critical Care Medicine

Topic

Cystic Fibrosis Research Advances

Field

Medicine

Canadian institutions

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Funders

Bayer HealthCareTenovusWellcome TrustAlereCystic Fibrosis Foundation TherapeuticsGlaxoSmithKlineQueen's University BelfastAstraZenecaQueen's UniversityEuropean Respiratory SocietyPfizer

Keywords

BronchiectasisMedicineSputumInternal medicineDesmosineNeutrophil elastaseGastroenterologyPulmonary function testingElastaseExacerbationProspective cohort studyLungPathologyElastinTuberculosis

Has abstract in OpenAlex

yes

API

/api/v1/works/W2560738370