Relationship between Symptoms, Exacerbations, and Treatment Response in Bronchiectasis

Abstract

<b>Rationale:</b> Bronchiectasis guidelines regard treatment to prevent exacerbation and treatment of daily symptoms as separate objectives.<b>Objectives:</b> 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.<b>Methods:</b> 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 <i>post hoc</i> analysis of a randomized trial of inhaled dry powder mannitol (<i>N</i> = 461 patients).<b>Measurements and Main Results:</b> 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; <i>P</i> = 0.005). Patients with higher symptom scores had higher exacerbation rates (RR, 1.74; 95% CI, 1.12-2.72; <i>P</i> = 0.01) over 12-month follow-up than those with lower symptoms. Inhaled mannitol treatment improved the time to first exacerbation (hazard ratio, 0.56; 95% CI, 0.40-0.77; <i>P</i> < 0.001), and the proportion of patients remaining exacerbation free for 12 months of treatment was higher in the mannitol group (32.7% vs. 14.6%; RR, 2.84; 95% CI, 1.40-5.76; <i>P</i> = 0.003), but only in highly symptomatic patients. In contrast, no benefit was evident in patients with lower symptom burden.<b>Conclusions:</b> Highly symptomatic patients have increased risk of exacerbations, and exacerbation benefit with inhaled mannitol was only evident in patients with high symptom burden.