title: Association between lung function and exacerbation frequency in patients with COPD.
abstract: OBJECTIVE
  To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD.
  
  
  METHODS
  We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo. Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization. The association between the mean forced expiratory volume in one second (FEV(1))% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects. The regression equations were applied to the mean FEV(1)% predicted for each GOLD stage to estimate the frequency per stage.
  
  
  RESULTS
  Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations. Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD. Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively. For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively. Study duration or type of study (cohort versus trial) did not significantly affect the outcomes.
  
  
  CONCLUSIONS
  This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes.
authors.affiliation: Institute for Medical Technology Assessment, Erasmus University, Rotterdam. hoogendoorn@bmg.eur.nl
authors.forename: Martine
authors.initials: M
authors.lastname: Hoogendoorn
authors.forename: Talitha L
authors.initials: TL
authors.lastname: Feenstra
authors.forename: Rudolf T
authors.initials: RT
authors.lastname: Hoogenveen
authors.forename: Maiwenn
authors.initials: M
authors.lastname: Al
authors.forename: Maureen Rutten-van
authors.initials: MR
authors.lastname: Mölken
mesh_terms: D000368:Aged; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016014:Linear Models; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D013147:Spirometry; D016896:Treatment Outcome