Characterization of the “Frequent Exacerbator Phenotype” in Bronchiectasis

Rationale: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of frequently exacerbating patients are not well described.Objectives: To establish if there is a "frequent exacerbator phenotype" in bronchiectasis and the impact of exacerbations on long-term clinical outcomes. Methods:We studied bronchiectasis patients enrolled from 10 clinical centres in Europe and Israel, with up to 5-years follow-up.Patients were categorized by baseline exacerbation frequency (0, 1, 2 or >3 per year).The repeatability of exacerbation status was assessed as well as the independent impact of exacerbation history on hospitalizations, quality of life and mortality. Measurements and Main Results:2572 patients were included.Frequent exacerbations were the strongest predictor of future exacerbation frequency suggesting a consistent "phenotype".The incident rate ratios for future exacerbations were 1.73 (95%CI 1.47-2.02,p<0.0001) for 1 exacerbation per year, 3.14 (95%CI 2.70-3.66,p<0.0001) for 2 exacerbations and 5.97 (95%CI 5.27-6.78,p<0.0001) for patients with >3 exacerbations per year at baseline.Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, forced expiratory volume in 1 second, radiological severity of disease and co-existing COPD.Frequently exacerbating patients had worse quality of life and were more likely to be hospitalized during follow-up.Mortality over up to 5 years follow-up increased with increasing exacerbation frequency.Conclusions: The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life and increased mortality during follow-up.