Disease Trajectories and Impact of One Moderate Exacerbation in Gold B COPD Patients

Introduction: Studies have shown that exacerbation in chronic obstructive pulmonary disease (COPD) increases the risk of further exacerbations. Our aim was to investigate the impact of a single moderate exacerbation on the odds of subsequent exacerbations and death in GOLD B COPD patients. Methods: This hospital-based nationwide, cohort study in Denmark included all patients >40 years of age with an in-and/or outpatient ICD-10 J44 diagnosis (COPD Register, 2008-2014). Index was date of first registered modified Medical Research Council (mMRC) score >2; baseline period was 12 months pre-index. At index, patients were grouped as: B0, no exacerbation; and B1, one moderate exacerbation during the previous year, and followed for three consecutive years in 2008-2017 for development of moderate (short-term use of prednisolone or prednisone) and severe (emergency visit or hospitalization) exacerbations and death. Using B0 as reference, the odds ratio (OR) for exacerbation and death in GOLD B1 was estimated with multinominal logistic regression and a Cox model estimated the hazard ratio for exacerbation accounting for recurrent events. Results: In total, 8,453 patients (mean age 70 years, 51% male) were included, of which GOLD B0 4,545 and GOLD B1 3,908 patients. During the 3-year follow-up, 34.1% and 24.9% of GOLD B0 and B1, respectively, had none or one moderate exacerbation whereas 61.9% and 71.2% of B0 and B1, respectively, had a severe trajectory with multiple moderate and/or a severe exacerbation or died. In B1 patients, the OR for 1 moderate, >2 moderate exacerbations, >1 severe exacerbation was 1.58 [CI 1.33-1.87], 2.60 [2.19- 3.08], 2.08 [1.76-2.45], respectively, and 1.85 [1.57-2.17] for death compared with B0. Conclusion: One moderate exacerbation in COPD patients with high symptom burden increases the odds of subsequent exacerbations and death during the three following years. The results emphasize the importance of preventing exacerbations in GOLD B patients.