Long-term outcomes following first short-term clinically important deterioration in COPD

Respir Res. 2018 Nov 20;19(1):222. doi: 10.1186/s12931-018-0928-3.


Background: Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline. Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed. We evaluated post hoc the link between early CID and long-term adverse outcomes.

Methods: CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥4-unit increase in St George's Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies. Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE). Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.

Results: In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+. At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001). Similar risks post-CID were observed in ECLIPSE.

Conclusions: A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors.

Trial registration: NCT00268216 ; NCT00292552 .

Keywords: COPD; Clinically important deterioration; Composite measures; Mortality.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Bronchodilator Agents / administration & dosage*
  • Clinical Deterioration*
  • Disease Progression
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume / drug effects
  • Forced Expiratory Volume / physiology*
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Retrospective Studies
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome


  • Bronchodilator Agents

Associated data

  • ClinicalTrials.gov/NCT00268216
  • ClinicalTrials.gov/NCT00292552