Bronchiectasis: new therapies and new perspectives

Abstract

European Respiratory Society guidelines for the management of adult bronchiectasis highlight the paucity of treatment options available for patients with this disorder. No treatments have been licensed by regulatory agencies worldwide, and most therapies used in clinical practice are based on very little evidence. Development of new treatments is needed urgently. We did a systematic review of scientific literature and clinical trial registries to identify agents in early-to-late clinical development for bronchiectasis in adults. In this Review, we discuss the mechanisms and potential roles of emerging therapies, including drugs that target airway and systemic inflammation, mucociliary clearance, and epithelial dysfunction. To ensure these treatments achieve success in randomised clinical trials-and therefore reach patients-we propose a reassessment of the current approach to bronchiectasis. Although understanding of the pathophysiology of bronchiectasis is at an early stage, we argue that bronchiectasis is a heterogeneous disease with many different biological mechanisms that drive disease progression (endotypes), and therefore the so-called treatable traits approach used in asthma and chronic obstructive pulmonary disease could be applied to bronchiectasis, with future trials targeted at the specific disease subgroups most likely to benefit.

Twenty‐five years of Respirology: Advances in bronchiectasis

“…Bronchiectasis, a silent emerging global epidemic, has experienced a clinical and research renaissance over the last decade . Increased access to radiology, physician awareness and its overlap with other chronic respiratory disease states has brought renewed attention to this neglected disease .…”

“…Australia‐New Zealand, United Kingdom and Saudi Arabia) and the European Respiratory Society (ERS) published the first international guidelines informing management of adults with bronchiectasis. These publications highlight the lack of licensed treatment for patients with bronchiectasis and the substantial deficiencies in our understanding of its epidemiology, pathophysiology, heterogeneity and treatment . Despite this, key advances in each of these areas have occurred and our understanding of disease, particularly affecting the Asia‐Pacific region, continues to advance.…”

“…Significant ethno‐geographic variation in aetiology, microbiology and clinical approach further poses a significant challenge to translating research findings into practice and, while severity scoring systems are established in adults, no validated biomarkers currently exist assessing disease severity, progression and/or exacerbations. Advances that have focused on neutrophil elastase activity and serum desmosine (including point‐of‐care testing for patient stratification) in bronchiectasis have shown promise …”

“…Despite a current lack of evidence‐based pharmaceutical therapy for bronchiectasis, advances in identifying ‘treatable’ (therapeutic) and ‘targetable’ (endo‐phenotypic) traits have occurred . This approach has been successfully exploited in asthma and chronic obstructive pulmonary disease (COPD) but not yet bronchiectasis.…”

“…This approach has been successfully exploited in asthma and chronic obstructive pulmonary disease (COPD) but not yet bronchiectasis. Novel experimental treatments targeting the bone marrow with cathepsin C/diacylglycerol diphosphate phosphatase 1 (DPP1) inhibitors, ion channels with epithelial sodium channel (ENaC) inhibition or cystic fibrosis transmembrane conductance regulator (CFTR) correction and inflammation with C‐X‐C motif chemokine receptor 2 (CXCR2) or neutrophil elastase inhibitors have been proposed but lack evidence . Elucidating endo‐phenotypic features in particular patients may be key, for instance, eosinophilic airway predominance (present in up to one‐quarter) of bronchiectasis adults permits the potential use of available and licensed drugs targeting eosinophil recruitment and function including inhaled corticosteroids, anti‐interleukin (IL)‐5 and anti‐IL‐13 …”