The frequent exacerbator phenotype in bronchiectasis revisited: data from EMBARC registry

Rationale: The frequent exacerbator phenotype was previously defined using a threshold of  ≥3 exacerbations per year in bronchiectasis. However, the contribution of each prior exacerbation to future risk as well as the influence of severe exacerbations and different etiologies and regions remain poorly understood. Objectives: To quantify the risk associated with each prior exacerbation of bronchiectasis in predicting future exacerbations and severe exacerbations, and to determine whether this association varies across different etiologies and geographic regions. Methods: We analyzed data from the European Bronchiectasis Registry (EMBARC), including 30 countries across Europe and Asia. The association between baseline exacerbation history and future exacerbations was tested using negative binomial regression over up to 5 years of follow-up. Severe exacerbations were defined as those requiring hospitalization. Measurements and main results: A total of 19 324 patients with bronchiectasis were included. Each prior exacerbation was associated with an increased risk of exacerbations and severe exacerbations. Incidence rate ratio (IRR) for future exacerbations was 1.45 (95% CI 1.34-1.58, P < .001) for 1 exacerbation; 1.84 (95% CI 1.69-1.99, P < .001) for 2 exacerbations; 2.50 (95% CI 2.29-2.73, P < .001) for 3 exacerbations; and 3.56 (95% CI 3.32-3.82, P < .001) for patients with 4 or more prior exacerbations. Additionally, 1 prior severe exacerbation was associated with increased risk of exacerbation (IRR = 1.52, 95% CI 1.45-1.60, P < .001) and strongly associated with future severe exacerbations (IRR = 3.96, 95% CI 3.71-4.22, P < .001). The frequent exacerbator phenotype was consistent across different etiologies and geographic regions. Conclusions: The frequent exacerbator phenotype is highly consistent across patient subgroups and regions. Each prior exacerbation is associated with a progressively higher risk, with no definitive threshold-defining high risk.