Background: In contemporary management of COPD, the frequent exacerbator phenotype based on a 12-month history of acute exacerbations (AECOPD) is a major determinant of therapeutic recommendations. However, there is considerable debate on the stability of this phenotype over time.

Methods: We used fundamental principles in time-to-event analysis to demonstrate that variation in the frequent exacerbator phenotype has two major sources: variability in the underlying AECOPD rate and the randomness in the occurrence of individual AECOPDs. We re-analysed data from two large cohorts (ECLIPSE and SPIROMICS) using a Bayesian model that separated these sources of variability. We then evaluated the stability of the frequent exacerbator phenotype based on these results.

Results: In both cohorts, the pattern of AECOPDs strongly supported the presence of an individual-specific underlying AECOPD rate which is stable over time (Bayes Factor <0.001). Despite this, the observed AECOPD rate can markedly vary year-to-year within individual patients. For those with an underlying rate between 0.8-3.1/year, the frequent exacerbator classification, based on the observed rate, changes >30% of the time over two consecutive years due to chance alone. This value increases to >45% for those with an underlying rate between 1.2-2.2/year.

Conclusion: While the underlying AECOPD rate is a stable trait, the frequent exacerbator phenotype based on observed AECOPD patterns is unstable, so much so that its suitability for informing treatment decisions should be questioned. Whether evaluating AECOPD history over longer durations or the use of multivariate prediction models can result in more stable phenotyping needs to be evaluated.