title: The impact of exacerbation frequency on mortality following acute exacerbations of COPD: a registry-based cohort study.
abstract: OBJECTIVE
  To examine the association between exacerbation frequency and mortality following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
  
  
  METHODS
  Cohort study using medical databases.
  
  
  METHODS
  Northern Denmark.
  
  
  METHODS
  On 1 January 2005, we identified all patients with prevalent hospital-diagnosed chronic obstructive pulmonary disease (COPD) who had at least one AECOPD during 1 January 2005 to 31 December 2009. We followed patients from the first AECOPD during this period until death, emigration or 31 December 2009, whichever came first. We flagged all AECOPD events during follow-up and characterised each by the exacerbation frequency (0, 1, 2 or 3+) in the prior 12-month period.
  
  
  METHODS
  Using Cox regression, we computed 0-30-day and 31-365-day age-adjusted, sex-adjusted, and comorbidity-adjusted mortality rate ratios (MRRs) with 95% CIs entering exacerbation frequency as a time-varying exposure.
  
  
  RESULTS
  We identified 16,647 eligible patients with prevalent COPD, of whom 6664 (40%) developed an AECOPD and were thus included in the study cohort. The 0-30-day MRRs were 0.97 (95% CI 0.80 to 1.18), 0.90 (95% CI 0.70 to 1.15) and 1.03 (95% CI 0.81 to 1.32) among patients with AECOPD with 1, 2 and 3+ AECOPDs versus no AECOPD within the past 12 months, respectively. The corresponding MRRs were 1.47 (95% CI 1.30 to 1.66), 1.89 (95% CI 1.59 to 2.25) and 1.59 (95% CI 1.23 to 2.05) for days 31-365.
  
  
  CONCLUSIONS
  Among patients with AECOPD, one or more exacerbations in the previous year were not associated with 30-day mortality but were associated with an increased 31-365-day mortality.
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors.forename: Sigrun Alba Johannesdottir
authors.initials: SA
authors.lastname: Schmidt
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors.forename: Martin Berg
authors.initials: MB
authors.lastname: Johansen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Olsen
authors.affiliation: AstraZeneca LP, Gaithersburg, Maryland, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Medimmune LLC, Gaithersburg, Maryland, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Parker
authors.affiliation: KaloBios Pharmaceuticals, Inc, South San Francisco, California, USA.
authors.forename: Nestor A
authors.initials: NA
authors.lastname: Molfino
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Lash
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors.forename: Christian Fynbo
authors.initials: CF
authors.lastname: Christiansen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000401:mortality*; D012042:Registries / Q000706:statistics & numerical data; D012044:Regression Analysis
keywords: Cohort study; Registry study; Severe exacerbations; Time-varying exposure