Susceptibility to Exacerbation in Chronic Obstructive Pulmonary Disease.

被引:2095
作者
Hurst, John R. [1 ]
Vestbo, Jorgen [2 ,3 ,4 ]
Anzueto, Antonio [7 ]
Locantore, Nicholas [8 ]
Muellerova, Hana [9 ]
Tal-Singer, Ruth [10 ]
Miller, Bruce [10 ]
Lomas, David A. [5 ]
Agusti, Alvar [11 ,12 ]
MacNee, William [13 ]
Calverley, Peter [6 ]
Rennard, Stephen [14 ]
Wouters, Emiel F. M. [15 ]
Wedzicha, Jadwiga A. [1 ]
机构
[1] UCL Med Sch, Acad Unit Resp Med, London, England
[2] Hvidovre Univ Hosp, Copenhagen, Denmark
[3] Univ Copenhagen, Copenhagen, Denmark
[4] Univ Manchester, Manchester Acad Hlth Sci Ctr, Sch Translat Med, Resp Res Grp, Manchester, Lancs, England
[5] Univ Cambridge, Dept Med, Cambridge Inst Med Res, Cambridge CB2 2QQ, England
[6] Univ Liverpool, Sch Clin Sci, Dept Resp Med, Liverpool L69 3BX, Merseyside, England
[7] Univ Texas Hlth Sci Ctr San Antonio, Pulm Sect, San Antonio, TX 78229 USA
[8] GlaxoSmithKline Inc, Res Triangle Pk, NC USA
[9] GlaxoSmithKline Inc, London, England
[10] GlaxoSmithKline Inc, King Of Prussia, PA USA
[11] Hosp Clin Barcelona, Inst Torax, CIBER Enfermedades Resp, Barcelona, Spain
[12] Fdn Caubet Cimera, Barcelona, Spain
[13] Univ Edinburgh, ELEGI Colt Res Labs, Queens Med Res Inst, MRC Ctr Inflammat Res, Edinburgh, Midlothian, Scotland
[14] Nebraska Med Ctr, Dept Pulm & Crit Care Med, Omaha, NE USA
[15] Maastricht Univ Med Ctr, Dept Resp Med, Maastricht, Netherlands
关键词
COPD EXACERBATIONS; INFLAMMATORY MARKERS; SYMPTOMS; POPULATION; DIAGNOSIS; COHORT;
D O I
10.1056/NEJMoa0909883
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.) N Engl J Med 2010;363:1128-38.
引用
收藏
页码:1128 / 1138
页数:11
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