Temporal Clustering of Exacerbations in Chronic Obstructive Pulmonary Disease

Abstract

Rationale: Exacerbations are important events in chronic obstructive pulmonary disease. Preventing exacerbations is a key treatment goal. Observational data suggest that after a first exacerbation, patients may be at increased risk of a second exacerbation, but this has not been specifically studied. We hypothesized that exacerbations may cluster together in time, a finding that would have important implications for targeting preventative interventions and the analysis of clinical trial data.Objectives: To assess whether exacerbations are random events, or cluster in time.Methods: A total of 297 patients in the London chronic obstructive pulmonary disease cohort recorded daily symptoms and were assessed for a total of 904 patient-years. The observed timing of second exacerbations after an initial exacerbation was compared with that expected should exacerbations occur randomly.Measurements and Main Results: The observed timing distribution of second exacerbations differed significantly (P < 0.001) from the...