Airway Disorders Network
Bronchiectasis is a condition of dilated, inflamed airways and mucous production caused by a myriad of diseases. Bronchiectasis entails chronic productive cough and an increased risk of infections leading to exacerbations. Chronic bacterial infections are often a hallmark of severe disease, especially with Pseudomonas aeruginosa (O’Donnell AE. N Engl J Med. 2022;387:533). Prophylactic inhaled antibiotics have been used as off-label therapies with mixed evidence, particularly in non-cystic fibrosis bronchiectasis (Rubin BK, et al. Respiration. 2014;88:177).
In a recent publication, Guan and colleagues evaluated the efficacy and safety of tobramycin inhaled solution (TIS) for bronchiectasis with chronic P. aeruginosa in a phase 3, 16-week, multicenter, double-blind randomized, controlled trial (Guan W-J, et al. Chest. 2023;163:64). A regimen of twice-daily TIS, compared with nebulized normal saline, demonstrated a more significant reduction in P. aeruginosa sputum density after two cycles of 28 days on-treatment and 28 days off-treatment (adjusted mean difference, 1.74 log10 colony-forming units/g; 95% CI, 1.12-2.35; (P < .001), and more patients became culture-negative for P. aeruginosa in the TIS group than in the placebo group on day 29 (29.3% vs 10.6%). Adverse events were similar in both groups. Importantly, there was an improvement in quality-of-life bronchiectasis respiratory symptom score by 7.91 points at day 29 and 6.72 points at day 85; all three were statistically significant but just below the minimal clinically important difference of 8 points.
Dr. Conroy Wong and Dr. Miguel Angel Martinez-Garcia (Chest. 2023 Jan;163:3) highlighted in their accompanying editorial that use of health-related quality of life score was a “distinguishing feature” of the trial as “most studies have used the change in microbial density as the primary outcome measure alone.”
Future studies evaluating cyclical vs continuous antibiotic administration, treatment duration, and impact on exacerbations continue to be needed.
Alicia Mirza, MD