Yong-Hua Gao1,2, Hani Abo Leyah2, Simon Finch2, Mike Lonergan2, Stefano Aliberti3, Anthony De Soyza4, Thomas C Fardon2, Gregory Tino5, James D Chalmers2. 1. Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 2. Scottish Centre for Respiratory Medicine, University of Dundee, Dundee, United Kingdom. 3. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 4. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; and. 5. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
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 exacerbation rates (RR, 1.74; 95% CI, 1.12-2.72; P = 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; P < 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; 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.
RCT Entities:
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 exacerbation rates (RR, 1.74; 95% CI, 1.12-2.72; P = 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; P < 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; 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.