Introduction: Prior exacerbations are the main risk factor for exacerbations in bronchiectasis. Guidelines recommend macrolide only in frequent exacerbators. Other studies suggest that symptoms are related to increased exacerbation risk. We aimed to investigate if symptoms could independently predict future exacerbations and identify responders to long-term macrolide therapy.

Methods: Prospective observational study including 8328 patients from EMBARC registry with symptoms (Quality-of-life questionnaire Bronchiectasis (QoL-B) at baseline) and follow-up for at least one year, and posthoc analysis of 3 randomized clinical trials (RCTs) of macrolides in 341 bronchiectasis patients.

Results: Prior exacerbations (RR for every exacerbation=1.10, 95%CI 1.09-1.11, p<0.001) and symptoms (RR for every 10 points lower QoL-B=1.10, 95%CI 1.08-1.11, p<0.001) were identified as independent risk factors for future exacerbations in the EMBARC registry. The expected number of exacerbations in 1-year was similar between the group with 3 prior exacerbations and average symptom scores (1.49, 95% CI 1.38-1.60) and the group with no prior exacerbations but high symptom scores (1.47, 95% CI 1.34-1.60). The same pattern was observed in the post-hoc analysis of RCTs, both in macrolide and placebo arms. The number needed to treat to prevent exacerbations with macrolides was similar among patients selected based on frequent exacerbations and in those with no prior/few exacerbations but high symptom scores.

Conclusion: Symptoms are an independent risk factor for exacerbations in bronchiectasis, and highly symptomatic patients may benefit from long-term macrolides.