Predicting Re-Exacerbation Timing and Understanding Prolonged Exacerbations: An Analysis of Patients with COPD in the ECLIPSE Cohort

PURPOSE: Understanding risk factors for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is important for optimizing patient care. We re-analyzed data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study (NCT00292552) to identify factors predictive of re-exacerbations and associated with prolonged AECOPDs. METHODS: Patients with COPD from ECLIPSE with moderate/severe AECOPDs were included. The end of the first exacerbation was the index date. Timing of re-exacerbation risk was assessed in patients with 180 days’ post-index-date follow-up data. Factors predictive of early (1–90 days) vs late (91–180 days) vs no re-exacerbation were identified using a multivariable partial-proportional-odds-predictive model. Explanatory logistic-regression modeling identified factors associated with prolonged AECOPDs. RESULTS: Of the 1,554 eligible patients from ECLIPSE, 1,420 had 180 days’ follow-up data: more patients experienced early (30.9%) than late (18.7%) re-exacerbations; 50.4% had no re-exacerbation within 180 days. Lower post-bronchodilator FEV(1) (P=0.0019), a higher number of moderate/severe exacerbations on/before index date (P<0.0001), higher St. George’s Respiratory Questionnaire total score (P=0.0036), and season of index exacerbation (autumn vs winter, P=0.00164) were identified as predictors of early (vs late/none) re-exacerbation risk within 180 days. Similarly, these were all predictors of any (vs none) re-exacerbation risk within 180 days. Median moderate/severe AECOPD duration was 12 days; 22.7% of patients experienced a prolonged AECOPD. The odds of experiencing a prolonged AECOPD were greater for severe vs moderate AECOPDs (adjusted odds ratio=1.917, P=0.002) and lower for spring vs winter AECOPDs (adjusted odds ratio=0.578, P=0.017). CONCLUSION: Prior exacerbation history, reduced lung function, poorer respiratory-related quality-of-life (greater disease burden), and season may help identify patients who will re-exacerbate within 90 days of an AECOPD. Severe AECOPDs and winter AECOPDs are likely to be prolonged and may require close monitoring.