title: Susceptibility to exacerbation in chronic obstructive pulmonary disease.
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.)
authors.affiliation: Academic Unit of Respiratory Medicine, Royal Free Campus, UCL Medical School, London, United Kingdom.
authors.forename: John R
authors.initials: JR
authors.lastname: Hurst
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.forename: Nicholas
authors.initials: N
authors.lastname: Locantore
authors.forename: Hana
authors.initials: H
authors.lastname: Müllerova
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.forename: Bruce
authors.initials: B
authors.lastname: Miller
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Alvar
authors.initials: A
authors.lastname: Agusti
authors.forename: William
authors.initials: W
authors.lastname: Macnee
authors.forename: Peter
authors.initials: P
authors.lastname: Calverley
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennard
authors.forename: Emiel F M
authors.initials: EF
authors.lastname: Wouters
authors.forename: Jadwiga A
authors.initials: JA
authors.lastname: Wedzicha
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000145:classification / Q000188:drug therapy / Q000503:physiopathology*; D012008:Recurrence; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents