title: Markers of exacerbation severity in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Patients with chronic obstructive pulmonary disease (COPD) can experience 'exacerbations' of their conditions. An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management. There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies. Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD. In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event.
  
  
  METHODS
  We have searched standard databases between 1966 to July 2004 using major keywords and terms. Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study. Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria. Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I) and in-patient (Levels II & III combined). For both approaches, we performed a fixed effect meta-analysis on each of the reported variables.
  
  
  RESULTS
  We included a total of 268 studies reported between 1979 to July 2004. These studies investigated 142,407 patients with COPD. Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings. Most other measures showed weak relationships with either level or setting, or they had insufficient data to permit meta-analysis.
  
  
  CONCLUSIONS
  Arterial carbon dioxide and breathing rate varied in a consistent manner with exacerbation severity and patient setting. Many other measures showed weak correlations that should be further explored in future longitudinal studies or assessed using suggested mathematical modelling techniques.
authors: Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands. l.franciosi@telus.net
authors: Luigi G
authors: LG
authors: Franciosi
authors: Clive P
authors: CP
authors: Page
authors: Bartolome R
authors: BR
authors: Celli
authors: Mario
authors: M
authors: Cazzola
authors: Michael J
authors: MJ
authors: Walker
authors: Meindert
authors: M
authors: Danhof
authors: Klaus F
authors: KF
authors: Rabe
authors: Oscar E
authors: OE
authors: Della Pasqua