Characterization of the “Frequent Exacerbator Phenotype” in Bronchiectasis

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Abstract

Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described.

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Most cited references 7

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Susceptibility to exacerbation in chronic obstructive pulmonary disease.

John R. Hurst, Jørgen Vestbo, Antonio Anzueto … (2010)

Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)

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Should we view chronic obstructive pulmonary disease differently after ECLIPSE? A clinical perspective from the study team.

Jørgen Vestbo, Àlvar Agustí, Emiel F. M. Wouters … (2014)

Chronic obstructive pulmonary disease (COPD) seems to be a heterogeneous disease with a variable course. We wished to characterize the heterogeneity and variability of COPD longitudinally. In the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study of 2,164 patients with clinically stable COPD, 337 smokers with normal lung function, and 245 never-smokers, we measured a large number of clinical parameters, lung function, exercise tolerance, biomarkers, and amount of emphysema by computed tomography. All three groups were followed for 3 years. We found a striking heterogeneity among patients with COPD, with poor correlations between FEV1, symptoms, quality of life, functional outcomes, and biomarkers. Presence of systemic inflammation was found in only a limited proportion of patients, and did not relate to baseline characteristics or disease progression, but added prognostic value for predicting mortality. Exacerbations tracked over time and added to the concept of the "frequent exacerbator phenotype." Disease course was very variable, with close to a third of patients not progressing at all. Risk factors for 3-year change in both FEV1 and lung density were assessed. For FEV1 decline, continued smoking and presence of emphysema were the strongest predictors of progression; club cell protein was found to be a potential biomarker for disease activity. For progression of emphysema, the strongest predictors were continued smoking and female sex. By following a large, well characterized cohort of patients with COPD over 3 years, we have a clearer picture of a heterogeneous disease with clinically important subtypes ("phenotypes") and a variable and not inherently progressive course. Clinical trial registered with www.clinicaltrials.gov (NCT00292552).

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Detection and severity grading of COPD exacerbations using the exacerbations of chronic pulmonary disease tool (EXACT).

Alex Mackay, Gavin C. Donaldson, Anant Patel … (2014)

Uncertainty exists over the ability of the exacerbations of chronic pulmonary disease tool (EXACT) patient-reported outcome diary to quantify exacerbation severity and frequency. To clarify this, we investigated the ability of the EXACT to assess severity of exacerbations and examined the relationship between exacerbations diagnosed using London chronic obstructive pulmonary disease (COPD) cohort diary cards, physician review and symptom-defined events using the EXACT. 58 patients enrolled in the London Chronic Obstructive Pulmonary Disease (COPD) cohort prospectively completed the EXACT during 128 cohort diary card-defined exacerbations between January 2010 and April 2012. Mean ± sd EXACT scores increased from 42.6 ± 8.6 at baseline to 48.0 ± 8.6 at exacerbation onset (p<0.001), and rose further to a maximum score of 54.1 ± 8.9. Maximum EXACT scores were significantly higher in treated than untreated events. Time taken for EXACT scores to return to baseline was significantly related to symptom recovery time as judged by London COPD cohort diary cards, and to peak expiratory flow rate recovery. ∼50% of both diary card-defined and healthcare utilisation exacerbations crossed the EXACT event threshold. However, only 27.9% of diary card-defined and 34.6% of healthcare utilisation exacerbations fully met the criteria for an EXACT event. Patients exhibited smaller rises in the EXACT score at exacerbation as baseline disease severity increased. The EXACT is an effective method of evaluating chronic obstructive pulmonary disease exacerbation severity. However, concerns remain about the ability of the EXACT to accurately detect exacerbations.

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Author and article information

Journal

Title: American Journal of Respiratory and Critical Care Medicine

Abbreviated Title: Am J Respir Crit Care Med

Publisher: American Thoracic Society

ISSN (Print): 1073-449X

ISSN (Electronic): 1535-4970

Publication date Created: June 2018

Publication date (Print): June 2018

Volume: 197

Issue: 11

Pages: 1410-1420

Affiliations

[1 ]Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom

[2 ]Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

[3 ]Internal Medicine Department, Respiratory Unit, and Cystic Fibrosis Adult Center, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

[4 ]Bayer AG, Berlin, Germany

[5 ]Pulmonary Institute, Carmel Medical Center, Haifa, Israel

[6 ]Respiratory Medicine, University Hospital Gasthuisberg, Leuven, Belgium

[7 ]Respiratory Disease, AZ Nikolaas, Sint-Niklaas, Belgium

[8 ]Royal Infirmary of Edinburgh, Edinburgh, United Kingdom

[9 ]University of Edinburgh, Edinburgh, United Kingdom

[10 ]Institute for Pulmonary Diseases of Vojvodina Sremska Kamenica and Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

[11 ]Gynecology, Obstetrics, and Reproductive Medicine, University of Saarland Medical School, Homburg/Saar, Germany

[12 ]Clinical Epidemiology and Medical Statistics Unit, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy

[13 ]Department of Respiratory Medicine, Galway University Hospitals, Galway, Ireland

[14 ]5th Department of Pulmonary Medicine, “Sotiria” Chest Diseases Hospital, Athens, Greece

[15 ]Servei de Pneumologia, Hospital Clinic, Institut D’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedade Respiratorias (CIBERES), Barcelona, Spain

[16 ]Adult Bronchiectasis Service and Sir William Leech Centre for Lung Research, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Heaton, United Kingdom; and

[17 ]Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

Article

DOI: 10.1164/rccm.201711-2202OC

PubMed ID: 29357265

SO-VID: fb0cfef2-572a-48bb-96e6-a80fdbc6afb8

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Characterization of the “Frequent Exacerbator Phenotype” in Bronchiectasis

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Most cited references 7

Susceptibility to exacerbation in chronic obstructive pulmonary disease.

Should we view chronic obstructive pulmonary disease differently after ECLIPSE? A clinical perspective from the study team.

Detection and severity grading of COPD exacerbations using the exacerbations of chronic pulmonary disease tool (EXACT).

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