Treatment with inhaled antibiotics in bronchiectasis, side effects, and evaluation of the tolerance test; analysis from the BATTLE randomized controlled trial

Abstract

Introduction: Tobramycin inhalation solution (TIS) is a treatment option for patients with frequent exacerbations of bronchiectasis. A possible side effect of TIS is the development of chronic cough and bronchospasm, whereby the guidelines suggest a (in hospital) tolerance test with the first dose of TIS. However, data on respiratory adverse events are not consistent. In the present analysis from the BATTLE study (NCT02657473), we evaluated the added value of the tolerance test and aimed to observe the development of inhaled treatment related bronchial hyperreactivity. Methods: Fifty-seven patients from the BATTLE study were analyzed. Patients were randomized to receive TIS or placebo OD for 1 year. A tolerance test was performed with spirometry measurements before and after the first dose and with a bronchodilator in advance. Adverse events were strictly monitored. Results: Fifty-seven patients (100%) passed the tolerance test with no decrease in spirometry measurements or development of local intolerability. During the study treatment, a total of five TIS-treated patients (17.8%) withdrew due to airway hyperresponsiveness after a mean of 9.2 (SD13.9) weeks and one placebo-treated patient (3.5%) after 2 weeks (TIS vs. placebo; p = 0.66). The other TIS-related adverse events were not clinically significant. Conclusion: The use of inhaled medication is well tolerated in the heterogenous bronchiectasis population, without signs of airway hyperresponsiveness after the first dose of inhaled medication. From this observation, it can be concluded that there is no additional value for this advised tolerance test. However, closely monitoring on adverse effects during the first weeks after starting TIS is recommended.