Yong-Hua Gao, Hani Abo Leyah, Simon Finch, Mike Lonergan, Stefano Aliberti, Anthony De Soyza, Thomas C Fardon, Gregory Tino, James D Chalmers

Link to publication page: https://www.atsjournals.org/doi/10.1164/rccm.201910-1972OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Journal Ref: Am J Respir Crit Care Med. 2020 Jun 15;201(12):1499-1507. PMID: 32097051 DOI: 10.1164/rccm.201910-1972OC

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.