Written by:
Global Project Leader, Early R&I, AstraZeneca
Executive Medical Director, Early R&I, AstraZeneca
Bronchiectasis is the third most common airway disease, behind asthma and COPD, yet very few people have ever heard of it.1 Through our research, we are aiming to better understand the infections that drive disease progression to develop novel treatment options that will help people to live better, healthier lives.
What is bronchiectasis?
Bronchiectasis is a chronic condition in which damaged airways in the lungs becoming widened and abnormally shaped. Despite its prevalence there is a relative lack of research focused on bronchiectasis meaning there is comparatively little understanding of how to effectively help patients. There is a critical unmet need in bronchiectasis, we currently have no licensed treatments and patients are typically assessed to have persistent symptoms and a poor quality of life.2
Like asthma and COPD, bronchiectasis is a heterogeneous disease meaning that symptoms, experiences and underlying biology can vary greatly between patients.3 Various causes for the disease have been identified, such as the genetic condition cystic fibrosis (CF),4 but the majority of cases are the result of factors such as immune diseases and infections such as pneumonia or tuberculosis.5 Of these non-CF cases, the causes of between 10 and 50% are still unexplained.6
In healthy lungs, the airways constantly produce mucus which helps to trap dirt and bacteria from the air. Specialised cells lining the airways carry the mucus out of the lungs, keeping the airways clear and removing anything the mucus traps. Widened and deformed airways are harder to clear and can become filled with mucus, providing an ideal place for bacteria to thrive.
The blocked airways reduce lung function and cause coughing and breathlessness which, together with the bacterial infections, further damage the airways, contributing to a cycle of worsening disease progression.7 Persistent bacterial infections also contribute to an increased rate of exacerbations and higher mortality.6,8
Our leading research in bronchiectasis
Our ambition is to deliver disease modification and achieve clinical remission in bronchiectasis by preventing chronic bacterial infections. Currently, these infections often require the intensive, specialist use of antibiotics to control.9 The need for antibiotics further increases the need for effective new treatments that will help to address the growing issue of antimicrobial resistance.
Pseudomonas aeruginosa (PsA) is a species of bacteria that is a leading cause of chronic lung infections in bronchiectasis.10 We are investigating medicines that could stop PsA from colonising the lungs and that the bacteria will be unable to develop resistance to. We are uniquely equipped to achieve this thanks to collaborations between our research teams that are experts in respiratory diseases and those that specialise in bacterial biology.
One of the challenges in targeting bacteria is that they can quickly change and evolve to develop resistance to treatments, as we have seen with most antibiotics. As such, we are following the science to uncover targets that the bacteria struggle to change. In addition, we are investigating treatments that hit multiple targets, making it even harder for the bacteria to develop resistance.
We have identified three aspects of the PsA colonisation process that are of interest for targeting therapies:
- Stop PsA from being able to attach to the surface of lung cells
- Block the ability of PsA to release toxins that cause inflammation and promote exacerbations
- Make PsA more vulnerable to attack by the immune system by preventing it from forming resistant colonies called biofilms.11
Professor James Chalmers, University of Dundee learns more about our approach to bronchiectasis from Christina Keen, VP and Head of Clinical Development and Rod Hughes, Executive Medical Director.
To understand the potential of these targets, we have analysed the genome of over 900 different PsA samples collected from all over the world between 2003 and 2014.12 Of these, more than 99.9% could be effectively treated by targeting the processes we are studying.
In addition, we are leading work to better understand the daily patient experience of living with bronchiectasis. This is helping to create a standardised way to monitor symptom severity and understand the frequency and impact of exacerbations, which can help to guide treatment approaches and develop better healthcare support. Following extensive research with clinicians and patients, we have designed a structured symptom diary which is being investigated for widespread use in clinical research and practice.
Shaping the future of care for bronchiectasis
For too long, the needs of people living with bronchiectasis have gone overlooked and unsupported by healthcare systems. Our unique combination of patient-centric, respiratory and microbiology expertise is enabling us to lead ground-breaking research in this space and is helping us to uncover novel therapeutic targets. By building on these successes, we aim to deliver medicines with the potential to achieve disease modification and remission with life-changing benefits for patients.
