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.
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.
Authors: Ali Roghanian; Ellen M Drost; William MacNee; Sarah E M Howie; Jean-Michel Sallenave Journal: Am J Respir Crit Care Med Date: 2006-09-07 Impact factor: 21.405
Authors: R William Vandivier; Valerie A Fadok; Peter R Hoffmann; Donna L Bratton; Churee Penvari; Kevin K Brown; Joseph D Brain; Frank J Accurso; Peter M Henson Journal: J Clin Invest Date: 2002-03 Impact factor: 14.808
Authors: Alexandra L Quittner; Anne E O'Donnell; Matthias A Salathe; Sandra A Lewis; Xiaoming Li; A Bruce Montgomery; Thomas G O'Riordan; Alan F Barker Journal: Thorax Date: 2014-10-16 Impact factor: 9.139
Authors: R Amitani; R Wilson; A Rutman; R Read; C Ward; D Burnett; R A Stockley; P J Cole Journal: Am J Respir Cell Mol Biol Date: 1991-01 Impact factor: 6.914
Authors: James D Chalmers; Maeve P Smith; Brian J McHugh; Cathy Doherty; John R Govan; Adam T Hill Journal: Am J Respir Crit Care Med Date: 2012-06-28 Impact factor: 21.405
Authors: Jan P Vandenbroucke; Erik von Elm; Douglas G Altman; Peter C Gøtzsche; Cynthia D Mulrow; Stuart J Pocock; Charles Poole; James J Schlesselman; Matthias Egger Journal: PLoS Med Date: 2007-10-16 Impact factor: 11.069
Authors: Pei Yee Tiew; Micheál Mac Aogáin; Soo Kai Ter; Stefano Aliberti; James D Chalmers; Sanjay H Chotirmall Journal: Mycopathologia Date: 2021-03-11 Impact factor: 2.574
Authors: Temperance R Rowell; James E Keating; Bryan T Zorn; Gary L Glish; Stephen B Shears; Robert Tarran Journal: Am J Physiol Lung Cell Mol Physiol Date: 2019-11-06 Impact factor: 5.464
Authors: Emeka B Okeke; Cameron Louttit; Chris Fry; Alireza Hassani Najafabadi; Kai Han; Jean Nemzek; James J Moon Journal: Biomaterials Date: 2020-02-03 Impact factor: 12.479
Authors: Megan J Webster; Boris Reidel; Chong D Tan; Arunava Ghosh; Neil E Alexis; Scott H Donaldson; Mehmet Kesimer; Carla M P Ribeiro; Robert Tarran Journal: Eur Respir J Date: 2018-10-04 Impact factor: 16.671
Authors: Terry L Ng; Amber Johnson; Raphael A Nemenoff; Elena Hsieh; Andrea Abeyta Osypuk; Adrie van Bokhoven; Howard Li; D Ross Camidge; Erin L Schenk Journal: J Thorac Oncol Date: 2020-12-09 Impact factor: 15.609
Authors: Martina Oriano; Francesco Amati; Andrea Gramegna; Anthony De Soyza; Marco Mantero; Oriol Sibila; Sanjay H Chotirmall; Antonio Voza; Paola Marchisio; Francesco Blasi; Stefano Aliberti Journal: Int J Mol Sci Date: 2021-06-01 Impact factor: 5.923
Authors: Carlos H Martinez; Yuka Okajima; Andrew Yen; Diego J Maselli; Pietro Nardelli; Farbord Rahaghi; Kendra Young; Gregory Kinney; Charles Hatt; Craig Galban; George R Washko; MeiLan Han; Raúl San José Estépar; Alejandro A Diaz Journal: Acad Radiol Date: 2020-03-23 Impact factor: 3.173