Precision medicine in bronchiectasis

Abstract

Bronchiectasis, due to its highly heterogenous nature, requires an individualised approach to therapy. Patients experience symptoms and exacerbations driven by a combination of impaired mucociliary clearance, airway inflammation and airway infection. Treatment of bronchiectasis aims to enhance airway clearance and to address the underlying causes of inflammation and infection susceptibility. Bronchiectasis has multiple causes and so the pathophysiology leading to individual symptoms and exacerbations are different between individuals. Standardised investigations are recommended by international guidelines to identify the underlying causes of bronchiectasis. The process of identifying the underlying biology within an individual is called "endotyping" and is an emerging concept across chronic diseases. Endotypes that have a specific treatment are referred to as "treatable traits" and a treatable traits approach to managing patients with bronchiectasis in a holistic and evidence-based manner is the key to improved outcomes. Bronchiectasis is an area of intense research. Endotyping allows identification of subsets of patients to allow medicines to be tested differently in the future where trials, rather than trying to achieve a "one size fits all" solution, can test efficacy in subsets of patients where the treatment is most likely to be efficacious.

Figure 1

Schematic of personalised therapy for bronchiectasis. The underlying cause is investigated by standardised testing. All patients are tested for immunodeficiency, ABPA and NTM. Specific subsets of patients are tested for PCD and CF while inflammatory bowel disease (IBD) is typically apparent from clinical history rather than requiring testing. Airway clearance is recommended for all patients after which subsequent pharmacotherapy is dependent on the presence of treatable traits, targeted to reduce frequent exacerbations or reduce symptoms. It is acknowledged that patients will often have both exacerbations and symptoms and some therapies are able to improve both aspects.