Emerging therapies in adult and paediatric bronchiectasis

Abstract

Bronchiectasis is a chronic respiratory disorder characterized by persistent productive cough and recurrent chest infections secondary to permanent structural airway damage. The current treatment strategies for this debilitating disorder are limited to prompt antibiotic treatment of infective exacerbations and regular airway clearance techniques. Despite its high morbidity and associated mortality across all age groups, it has been a neglected area of research in respiratory medicine and there remain no licensed disease‐modifying therapies. In this review, we have explored the numerous potential therapeutic targets to break the vicious cycle of infection and inflammation seen in these patients and the novel therapeutic agents that have been developed to target them. We have reviewed the role of novel anti‐inflammatory agents designed to target the persistent neutrophilic inflammatory infiltrate seen in bronchiectatic airways, including neutrophil elastase inhibitors, CXCR2 (CXC chemokine receptor 2) antagonists, DPP‐1 (dipeptidyl peptidase 1) inhibitors, PDE4 (phosphodiesterase 4) inhibitors and statins. Furthermore, we have explored novel targets to improve mucociliary clearance, namely ENaC (epithelial sodium channel) inhibitors, and discussed the potential of alternative antimicrobial strategies such as inhaled phages. Our review highlights the importance of a multi‐faceted approach to bronchiectasis management, which aims not only to eradicate or suppress bronchial infection but also to break the cycle of persistent airway inflammation that results in progressive lung damage in these patients.

Pathophysiology of Bronchiectasis

“…Downregulating ENaC has been suggested as a potential therapeutic strategy in both CF and PCD to reduce mucus viscosity and improve airway clearance. [43][44][45] The role of CFTR and CFTR mutations in bronchiectasis remains under debate in the literature, with conflicting studies being published. A study of 100 patients with idiopathic bronchiectasis in an Australian cohort found that the rate of classical CFTR mutations was 1:25, the same frequency as found in the general population.…”

Contemporary Concise Review 2018: Bronchiectasis

“…As previous studies on muscle training used different programmes, this promising intervention should be further evaluated in a larger study. Other emerging therapies in managing bronchiectasis, summarized in a recent review, include neutrophil elastase inhibitors, CXC chemokine receptor‐2 antagonists, dipeptidyl peptidase‐1 inhibitors, phosphodiesterase‐4 inhibitors, statins, epithelial sodium channel inhibitors and inhaled bacteriophages (as an alternative antimicrobial strategy), as depicted in Figure . To date, none are available.…”

“…non‐antibiotic macrolides) and neutrophilic killing (e.g. tamoxifen and protease‐activated receptor‐1 antagonist) may play a future role (Reproduced from Regan and Hill, with permission).…”

A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of Pseudomonas aeruginosa to the Native Quercetin

“…While the current approach of therapy is effective, the concern over the long-term use of inhaled antibiotics is that it will lead to the rise of antibiotic-resistant bacterial pathogens, resulting in worsened exacerbation of the disease [7,8]. For this reason, alternative treatment approaches that can break the vicious cycle of airways infection and inflammation have been actively investigated to complement antibiotic therapy [9].…”