Bronchiectasis - Emerging treatments

Inhaled ciprofloxacin

Inhaled ciprofloxacin led to a significantly longer time to exacerbation compared with placebo in one phase 3 clinical trial of patients with bronchiectasis and chronic Pseudomonas infection, but this was not supported in a second phase 3 trial or a pooled analysis.[116] A post-hoc analysis of both trials showed inhaled liposomal ciprofloxacin resulted in significant symptom improvements in patients during on-treatment periods, which were lost in off-treatment periods.[117] In one phase 3 trial, ciprofloxacin dry powder for inhalation for cycles of 14 days on/off over 48 weeks significantly prolonged time to first exacerbation versus pooled placebo and reduced the frequency of exacerbations compared with matching placebo.[118] In another phase 3 trial, trends toward clinical benefit were seen with ciprofloxacin dry powder for inhalation, but primary endpoints regarding exacerbations were not met.[119]

Nebulized amikacin

A prospective trial of nebulized amikacin showed a significant increase in the rate of bacterial eradication in sputum in patients with bronchiectasis.[120]

Nebulized aztreonam

Although initial trials of inhaled aztreonam failed to show benefit, a recent post-hoc analysis suggested that patients with the highest bacterial load may have improved quality of life when treated with inhaled aztreonam.[121]

Atorvastatin

A proof-of-concept study showed that atorvastatin reduced systemic inflammation and improved quality of life in patients with bronchiectasis who were infected with Pseudomonas aeruginosa.[122]

Brensocatib

Brensocatib is an oral dipeptidyl peptidase 1 (DPP-1) inhibitor that works by targeting the damaging effect of neutrophil serine proteases in bronchiectasis inflammation. In a phase 2, double-blind, randomized trial in patients with noncystic fibrosis bronchiectasis, it significantly prolonged time to first exacerbation compared with placebo. Adverse events of note included hyperkeratosis and increased dental pocket depth.[123] Brensocatib has been granted breakthrough therapy designation by the Food and Drug Administration.

Targeted treatment approaches

Compared with other respiratory conditions, such as cystic fibrosis and idiopathic pulmonary fibrosis, there is a general lack of evidence for effective treatments in bronchiectasis. Many clinical trials have failed to meet their primary end points and this could be driven by the heterogeneous nature of bronchiectasis with its many different causes and patient subgroups. In the future, there may be a move towards individualizing treatment by stratifying patients according to specific phenotypes. Examples of targetable traits include neutrophil dysfunction, protease-mediated lung damage, and changes in the airway microbiome.[124]