Performance of the EXAcerbations of chronic pulmonary disease tool patient-reported outcome measure in three clinical trials of chronic obstructive pulmonary disease

Ann Am Thorac Soc. 2014 Mar;11(3):316-25. doi: 10.1513/AnnalsATS.201309-305OC.


Rationale: The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) is a patient-reported outcome measure to standardize the symptomatic assessment of chronic obstructive pulmonary disease exacerbations, including reported and unreported events. The instrument has been validated in a short-term study of patients with acute exacerbation and stable disease; its performance in longer-term studies has not been assessed.

Objectives: To test the EXACT's performance in three randomized controlled trials and describe the relationship between resource-defined medically treated exacerbations (MTEs) and symptom (EXACT)-defined events.

Methods: Prespecified secondary analyses of data from phase II randomized controlled trials testing new drugs for the management of chronic obstructive pulmonary disease: one 6-month trial (United States) (n = 235) and two 3-month, multinational trials (AZ 1 [n = 749], AZ 2 [n = 597]). In each case, the experimental drugs were found to be ineffective, permitting assessment of the EXACT's performance in three independent studies of moderate to severe high-risk patients on maintenance therapies.

Measurements and main results: The mean age of subjects was 62 to 64 years; 48 to 76% were male. Mean FEV1 % predicted was 42 to 59%. EXACT scores exhibited internal consistency (Cronbach's α ≥ 0.90), reproducibility (intraclass correlation ≥ 0.70), correlation with St. George's Respiratory Questionnaire (Spearman rho [rs] = 0.62, 0.46, 0.46 in the three trials; P < 0.001), and Breathlessness Cough and Sputum Scale (AZ 1, rs = 0.83; AZ 2, rs = 0.83; P < 0.001). EXACT-defined events had a high correspondence with alternative indicators of worsening (94, 88, and 93%). In each trial, unreported events were similar in severity (mean EXACT score, 56, 57, 61 vs. 53, 54 [P < 0.05], 57 [P < 0.05], respectively; 100-point scale) and longer (median, 9, 8, 7 vs. 8, 7 [P < 0.01], 6 days, respectively) than moderate MTEs.

Conclusions: Data generated through the EXACT offers insight into the symptomatic nature of MTEs and the frequency, severity, and duration of unreported symptom-defined events. Clinical trials registered with (MPEX: NCT00739648; AZ 1: NCT00949975; AZ 2: NCT01023516).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Bronchodilator Agents / therapeutic use
  • Cohort Studies
  • Female
  • Humans
  • Levofloxacin / therapeutic use
  • Male
  • Medical Records*
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Pulmonary Disease, Chronic Obstructive / complications*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pyridones / therapeutic use
  • Reproducibility of Results
  • Severity of Illness Index
  • Sulfones / therapeutic use
  • Surveys and Questionnaires*
  • Time Factors


  • Anti-Bacterial Agents
  • Bronchodilator Agents
  • Pyridones
  • Sulfones
  • Levofloxacin
  • N-((5-(methanesulfonyl)pyridin-2-yl)methyl)-6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide

Associated data