Predictors of re-exacerbation after an index exacerbation of chronic obstructive pulmonary disease in the REDUCE randomised clinical trial

Abstract

BACKGROUND: Acute exacerbations of chronic obstruc-tive pulmonary disease (AECOPD) compromise physical activity and quality of life and contribute significantly to health care costs. Systemic glucocorticoids benefit clini-cal outcome in AECOPD, and the REDUCE trial demon-strated noninferiority of a 5-day treatment course with prednisone compared with 14 days therapy regarding clinical outcome over 6 months of follow-up. Unexpect-edly, we found an inverse correlation between circulat-ing cortisol levels and exacerbation risk during a 6-month follow-up period. OBJECTIVE: To evaluate whether additional predictors of COPD re-exacerbation can be identified after the index exacerbation in the REDUCE cohort. METHODS: Of 314 patients with AECOPD randomised to 5 or 14 days of prednisone treatment, 311 were included in the analysis. Parameters tested as predictors of re-ex-acerbation were sex, age, smoking status, forced expira-tory volume in one second (FEV1), dyspnoea as assessed with the Medical Research Council (MRC) dyspnoea scale, home oxygen therapy, pretreatment with sys-temic glucocorticoids, pretreatment with antibiotics, duration of hospitalisation, blood pressure, oxygen sat-uration, admission to the Intensive Care Unit (ICU) and relevant infections in follow-up. The risks for re-exacer-bation were estimated by means of logistic regression and Cox proportional hazard models and expressed as odds ratios and hazard ratios, respectively. RESULTS: After multivariate adjustment, significant pre-dictors at hospital discharge for COPD re-exacerbation during follow-up were: duration of hospital stay >8 days (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.03-2.28); FEV1 <30% predicted (HR 1.76, 95% CI 1.06-2.91); hypertension (HR 2.39, 95% CI 1.04-5.48) and MRC dyspnoea scale (HR 1.61, 95% CI 1.30-2.01, per unit increment). Present cigarette smoking (HR 0.60, 95% CI 0.38-0.92) was negatively associated with re-ex-acerbation. CONCLUSION: In addition to biochemical suppression of the adrenal glands, other standard clinical parameters predict re-exacerbation in patients admitted to the emergency department with AECOPD. (REDUCE trial registration: ISRCTN29646069).