The Relationship Between Symptoms, Exacerbations and Treatment Response in Bronchiectasis

RATIONALE: Bronchiectasis guidelines regard treatment to prevent exacerbation and treatment of daily symptoms as separate objectives. OBJECTIVE: We hypothesized that patients with greater symptoms would be at higher risk of exacerbations and therefore a treatment aimed at reducing daily symptoms would also reduce exacerbations in highly symptomatic patients. METHODS: An observational cohort of 333 patients from the East of Scotland(2012-2016). Symptoms were either modelled as a continuous variable or patients were classified as high, moderate and low symptom burden(>70, 40-70 and <40 using the SGRQ symptom score). We hypothesised that exacerbation would be reduced in highly symptomatic patients. This was tested in a post-hoc analysis of a randomized trial of inhaled mannitol (N=461 patients) Measurement and Main Results: In the observational cohort daily symptoms were a significant predictor of future exacerbations (rate ratio [RR] 1.10, 95% confidence interval[CI] 1.03-1.17, P=0.005). Patients with high symptom scores had higher exacerbation rates (RR 1.74, 95% CI 1.12-2.72,P=0.01) over 12 months follow-up compared to those with lower symptoms. Inhaled mannitol treatment improved the time to first exacerbation (hazard ratio [HR] 0.56; 95% CI 0.40-0.77; P<0.001) and the proportion of patients remaining exacerbation free for 12 months treatment was higher in the mannitol group (32.7% vs. 14.6%; RR 2.84, 95% CI 1.40-5.76; P=0.003) only in highly symptomatic patients. In contrast no benefit was evident in patients with lower symptom burden. CONCLUSIONS: Highly symptomatic patients are at increased risk of exacerbations, and exacerbation benefit with inhaled mannitol was only evident in patients with high symptom burden.