Discriminative Performance and Clinical utility of COPD Exacerbation Categories for Predicting Future Exacerbations

RATIONALE: Treatment initiation or intensification to prevent exacerbation of chronic obstructive pulmonary disease (COPD) is based on the identification of patients with high exacerbation risk. The commonly used high-risk category of at least 2 moderate or 1 severe exacerbation within the prior 12 months has limited supporting evidence. OBJECTIVE: To test the discriminative performance and assess the clinical utility of various COPD exacerbation categories for predicting future exacerbations. METHODS: In the COPDGene and NOVELTY cohorts, for each 1-year and 2-year recall periods, we estimated 6 distinct categories of exacerbation frequencies (based on distinct combinations of the number of moderate and severe events), each ascertained in 3 ways: within 1 year, in each of 2 consecutive years, and over a rolling combined 2-year period. We estimated the area under the receiver operating characteristic curve (AUC) and net benefit to evaluate, respectively, the discriminative performance and clinical utility of the resulting 18 categories for predicting the occurrence of two moderate or one severe exacerbation in the next 12 months. MEASUREMENTS AND MAIN RESULTS: In both COPDGene (n = 3,035) and NOVELTY (n = 3,080), the category of any moderate or severe exacerbation in the past two years had the highest AUC (COPDGene: 0.69, 95%CI 0.67-0.71; NOVELTY: 0.87, 95%CI 0.85-0.88) for predicting the outcome. The AUC was significantly higher than that of the current standard of care of ≥ 2 moderate or ≥ 1 severe exacerbations in the past year (ΔAUC = 0.03 in COPDGene and 0.12 in NOVELTY; both P < .001). In net benefit analysis, exacerbation patterns defined over rolling two-year windows provided the highest net benefit across a clinically relevant treatment threshold range of 5% to 30%. CONCLUSIONS: At least 1 moderate or 1 severe exacerbation over the previous 2 years has the highest discrimination and confers the highest clinical utility for predicting high COPD exacerbation risk.