Susceptibility to exacerbation in chronic obstructive pulmonary disease

John R. Hurst, Jørgen Vestbo, Antonio R Anzueto, Nicholas Locantore, Hana Müllerova, Ruth Tal-Singer, Bruce Miller, David A. Lomas, Alvar Agusti, William MacNee, Peter Calverley, Stephen Rennard, Emiel F M Wouters, Jadwiga A. Wedzicha

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.)

Original languageEnglish (US)
Pages (from-to)1128-1138
Number of pages11
JournalNew England Journal of Medicine
Volume363
Issue number12
DOIs
StatePublished - Sep 16 2010

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Chronic Obstructive Pulmonary Disease
Phenotype
Heartburn
Gastroesophageal Reflux
Disease Progression
Adrenal Cortex Hormones
Hospitalization
Cell Count
Biomarkers
Quality of Life
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hurst, J. R., Vestbo, J., Anzueto, A. R., Locantore, N., Müllerova, H., Tal-Singer, R., ... Wedzicha, J. A. (2010). Susceptibility to exacerbation in chronic obstructive pulmonary disease. New England Journal of Medicine, 363(12), 1128-1138. https://doi.org/10.1056/NEJMoa0909883

Susceptibility to exacerbation in chronic obstructive pulmonary disease. / Hurst, John R.; Vestbo, Jørgen; Anzueto, Antonio R; Locantore, Nicholas; Müllerova, Hana; Tal-Singer, Ruth; Miller, Bruce; Lomas, David A.; Agusti, Alvar; MacNee, William; Calverley, Peter; Rennard, Stephen; Wouters, Emiel F M; Wedzicha, Jadwiga A.

In: New England Journal of Medicine, Vol. 363, No. 12, 16.09.2010, p. 1128-1138.

Research output: Contribution to journalArticle

Hurst, JR, Vestbo, J, Anzueto, AR, Locantore, N, Müllerova, H, Tal-Singer, R, Miller, B, Lomas, DA, Agusti, A, MacNee, W, Calverley, P, Rennard, S, Wouters, EFM & Wedzicha, JA 2010, 'Susceptibility to exacerbation in chronic obstructive pulmonary disease', New England Journal of Medicine, vol. 363, no. 12, pp. 1128-1138. https://doi.org/10.1056/NEJMoa0909883
Hurst JR, Vestbo J, Anzueto AR, Locantore N, Müllerova H, Tal-Singer R et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. New England Journal of Medicine. 2010 Sep 16;363(12):1128-1138. https://doi.org/10.1056/NEJMoa0909883
Hurst, John R. ; Vestbo, Jørgen ; Anzueto, Antonio R ; Locantore, Nicholas ; Müllerova, Hana ; Tal-Singer, Ruth ; Miller, Bruce ; Lomas, David A. ; Agusti, Alvar ; MacNee, William ; Calverley, Peter ; Rennard, Stephen ; Wouters, Emiel F M ; Wedzicha, Jadwiga A. / Susceptibility to exacerbation in chronic obstructive pulmonary disease. In: New England Journal of Medicine. 2010 ; Vol. 363, No. 12. pp. 1128-1138.
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AU - Hurst, John R.

AU - Vestbo, Jørgen

AU - Anzueto, Antonio R

AU - Locantore, Nicholas

AU - Müllerova, Hana

AU - Tal-Singer, Ruth

AU - Miller, Bruce

AU - Lomas, David A.

AU - Agusti, Alvar

AU - MacNee, William

AU - Calverley, Peter

AU - Rennard, Stephen

AU - Wouters, Emiel F M

AU - Wedzicha, Jadwiga A.

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N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.)

AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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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