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. Objectives: We hypothesized that patients with greater symptoms would be at higher risk of exacerbations and therefore that a treatment aimed at reducing daily symptoms would also reduce exacerbations in highly symptomatic patients. Methods: Our study comprised an observational cohort of 333 patients from the East of Scotland (2012 2016). Either symptoms were modeled as a continuous variable or patients were classified as having high, moderate, or low symptom burden (.70, 40 70, and ,40 using the St. George s Respiratory Questionnaire symptom score). The hypothesis that exacerbation reductions would only be evident in highly symptomatic patients was tested in a post hoc analysis of a randomized trial of inhaled dry powder mannitol (N= 461 patients). Measurements 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 higher symptom scores had higher exacerbationrates (RR, 1.74;95%CI, 1.12 2.72;P = 0.01) over 12-month follow-up than thosewith lower symptoms. Inhaled mannitol treatment improved the time to first exacerbation (hazard ratio, 0.56; 95% CI, 0.40 0.77; P,0.001), and the proportion of patients remaining exacerbationfree for 12months of treatmentwas higher in themannitol group (32.7% vs. 14.6%; RR, 2.84; 95% CI, 1.40 5.76; P=0.003),but only in highly symptomatic patients. In contrast, no benefit was evident in patients with lower symptom burden. Conclusions: Highly symptomatic patients have increased risk of exacerbations, and exacerbation benefit with inhaled mannitol was only evident in patients with high symptom burden.