A comprehensive analysis of the impact of pseudomonas aeruginosa colonisation in adult bronchiectasis

Finch, Simon; Fardon, Tom; Friel, Melissa; Chalmers, James D.

doi:10.1183/13993003.congress-2015.oa471

Cited by 96 publications

(138 citation statements)

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“…We observed strong relationships between NE activity and bacterial load. NE activity was also highest in patients with P. aeruginosa infection, and this was consistent with previous studies in bronchiectasis that showed that bacteria, and P. aeruginosa in particular, were the key drivers of airway neutrophilic inflammation (22), and that that P. aeruginosa infection represented a distinct clinical phenotype associated with earlier mortality, more frequent exacerbations, and worse quality of life (14,22,29,30).…”

Section: Discussionsupporting

confidence: 78%

“…Quality of life was evaluated using the St. George's Respiratory Questionnaire (SGRQ) (21). Chronic infection was defined as the isolation of pathogens on at least 2 occasions 3 months apart during the preceding 12 months (22). Spirometry was performed according to American Thoracic Society/European Respiratory Society guidelines (23).…”

Section: Clinical Assessmentmentioning

confidence: 99%

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

Chalmers

Moffitt²,

Suárez-Cuartín

et al. 2017

Am J Respir Crit Care Med

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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 tomographyconfirmed 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 = 20.33; 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 (b coefficient, 20.139; 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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Section: Discussionsupporting

confidence: 78%

Section: Clinical Assessmentmentioning

confidence: 99%

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

Chalmers

Moffitt²,

Suárez-Cuartín

et al. 2017

Am J Respir Crit Care Med

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281

202

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“…P. aeruginosa colonisation defines a specific clinical phenotype of bronchiectasis, and is associated with a three-fold increase risk of death, a nearly seven-fold increase risk of hospital admissions, worse quality of life and more frequent exacerbations [27][28][29]. Evidence from CF suggests that attempts at eradication therapy targeting Pseudomonas can have success in converting patients to culture-negative status [30].…”

Section: Important Research Priorities Identified By Expertsmentioning

confidence: 99%

Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration

et al. 2016

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Bronchiectasis is a disease of renewed interest in light of an increase in prevalence and increasing burden on international healthcare systems. There are no licensed therapies, and large gaps in knowledge in terms of epidemiology, pathophysiology and therapy. The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) is a European Respiratory Society (ERS) Clinical Research Collaboration, funded by ERS to promote high-quality research in bronchiectasis. The objective of this consensus statement was to define research priorities in bronchiectasis. From 2014 to 2015, EMBARC used a modified Delphi process among European bronchiectasis experts to reach a consensus on 55 key research priorities in this field. During the same period, the European Lung Foundation collected 711 questionnaires from adult patients with bronchiectasis and their carers from 22 European countries reporting important research priorities from their perspective. This consensus statement reports recommendations for bronchiectasis research after integrating both physicians and patients priorities, as well as those uniquely identified by the two groups. Priorities identified in this consensus statement provide the clearest possible roadmap towards improving our understanding of the disease and the quality of care for patients with bronchiectasis. @ERSpublications EMBARC consensus statement identifies research priorities in bronchiectasis as determined by physicians and patients

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“…This results in marked differences in outcomes and treatment responses even within groups classified by a single feature, such as the presence of P. aeruginosa [19]. Future clinical trials for bronchiectasis must consider patient stratification and selection more closely including potential delineation based on airway inflammation and/ or specific components of the lung microbiome [11,[20][21][22].…”

mentioning

confidence: 99%

RESPIRE: breathing new life into bronchiectasis

Chotirmall

Chalmers

2018

Eur Respir J

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A comprehensive analysis of the impact of pseudomonas aeruginosa colonisation in adult bronchiectasis

Cited by 96 publications

References 0 publications

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

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

Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration

RESPIRE: breathing new life into bronchiectasis

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