Historically, what has the treatment and management of bronchiectasis in patients looked like?
Historically, bronchiectasis was a neglected disease with poor understanding of the aetiology and the underlying pathophysiology. The management options were limited with therapy focused on symptom relief. With advancement of medicine, the management of bronchiectasis shifted to targeting the underlying pathophysiology of bacterial infection, mucociliary dysfunction and airway inflammation. Bacterial infection was initially treated with oral antibiotics followed by the use airway devices to deliver the drugs locally in the airway. Another vital aspect of bronchiectasis treatment was the use of physiotherapy techniques to the improve mucociliary clearance, which in turn prevents bacterial growth. Pulmonary rehabilitation programmes were also developed to improve the patient’s quality of life.
Can you tell us a little more detail about the medicines commonly used today? What are some of the benefits and challenges in their use?
The current management of bronchiectasis is based on targeting the underlying pathophysiology of bronchiectasis. There are no licensed drug therapies for non-cystic fibrosis bronchiectasis, however many drugs have been repurposed to be used in bronchiectasis.
Acute infection (pulmonary exacerbations) are treated with oral/intravenous antibiotics with the antibiotic choice driven by sputum cultures wherever possible. Bronchiectasis patients can have chronic colonisation of the airways with bacteria, commonly Pseudomonas aeruginosa, which is treated with prophylactic oral or inhalational antibiotics. The aim is to reduce the number and severity of these exacerbations by targeting airway bacterial communities or associated airway inflammation.
Mucociliary dysfunction plays an important role in the pathogenesis of bronchiectasis and physiotherapy is the corner of treatment to improve mucociliary clearance and reduce exacerbations. Medications to aid mucociliary clearance include nebulised hypertonic saline and oral carbocisteine/acetylcysteine.
Novel drugs are being developed that target airway inflammation and are being tested through phase-2 and phase-3 clinical trials. Future guidelines will consider the emerging evidence for these therapies and where they may fit compared to current treatment strategies.
The current challenges in bronchiectasis treatment are liked with rising levels of antibiotic resistance, targeting airway inflammation with novel and personalised management therapies, and variable response to treatment due to heterogeneous endotypes and clinical phenotypes.
What are some of the findings in recent bronchiectasis research? What would you like to see the future of medicine in bronchiectasis look like?
Recent bronchiectasis research has been focused on all aspects of management of bronchiectasis including diagnosis, disease severity, phenotyping, genotyping and developing new targeted therapies. Two assessment tools have been developed to assess the severity of bronchiectasis (Bronchiectasis Severity Index and FACED score). Certain phenotype clusters have been identified such as those based on inflammation (neutrophilic or eosinophilic) or microbiological features (P. aeruginosa growth in sputum). These phenotypes have been associated with increased morbidity and mortality.
The results from the phase-2 WILLOW and the phase-3 ASPEN trial have been promising in reducing the frequency of pulmonary exacerbations in patients taking Brensocatib and might be the first licensed drug for bronchiectasis in the near future.
The future of medicine in bronchiectasis should be directed towards precision medicine with the use of omics technologies and identifying the role of biomarkers in the pathophysiology of bronchiectasis. In addition, preventing chronic airway inflammation which seems to drive the symptom burden in bronchiectasis needs to be addressed.
What impact could these developments have on patients and the wider health system?
The identification of biomarkers and disease endotypes will help investigators in enrolling patients to the right clinical trial and develop an individualised plan. The development of precision medicine will improve patient outcomes while reducing medication burden by omitting ineffective medications. Licensing of brensocatib for bronchiectasis will allow availability of the drug outside of clinical trial settings to the wider public. Improved patient outcomes, reduction in symptom burden and increased time to pulmonary exacerbations will ease the burden on the health system given the rising incidence of bronchiectasis worldwide.