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Using precision medicine to reduce unnecessary use of antibiotics for COPD flare-up

Dr Alexander Mathioudakis

Author: Dr Alexander Mathioudakis

NIHR Manchester BRC Clinical Fellow, Respiratory Theme

Twitter: @MathioudakisAG

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This is antibiotic awareness week but, it is fitting that it will shortly be followed by World COPD Day, as COPD exacerbations (“flare-ups”) represent one of the leading causes of inappropriate antibiotic administration.

Steroids are also significantly overused in COPD exacerbations. In the TRACE-COPD trial, we are using biomarkers (blood tests) to guide and target the administration of both antibiotics and oral steroids.

COPD is a burdensome, long-term lung disease causing persistent respiratory symptoms and narrowing of the airways. It is frequent, affecting more than one in ten people aged over 40 years, and according to the World Health Organisation it is the third leading cause of death globally. Patients with COPD often develop COPD exacerbations, which are symptom flare-ups causing poor health, hospitalisation or death. They are very frequent, as they are responsible for one in every eight hospital admission in the UK.

There are different types of exacerbations. Only about half of them, which are caused by bacteria (bugs) respond to antibiotics. Only 30-50% that are caused by inflammation of the airways with eosinophils (which are specific cells of the immune system) respond to oral steroids. And finally, up to 30% are caused by viruses and require antivirals. While we know that overuse of antibiotics can lead to the development of dangerous super-bugs and steroids can cause side effects, including severe infections, unfortunately, we do not have accurate tests to distinguish different types of COPD exacerbations. As a result, all exacerbations are treated the same, with inhaled medications called bronchodilators to open-up the airways, steroids to treat inflammation and almost invariably antibiotics, to treat infections. Therefore, both steroids and antibiotics are massively overused, posing unnecessary risks to patients with COPD.

In a recent systematic review, we found that procalcitonin, a biomarker in the blood, can point out those exacerbations that are caused by bacteria and would benefit from the administration of antibiotics. In addition, other studies showed that a subgroup of while blood cells, the blood eosinophil count, can identify exacerbations responding to systemic steroids. This provides a potential opportunity to personalise the management of COPD exacerbations, which could lead to improved use of healthcare resources and to a reduction in the frequency of unnecessary side effects and antibiotic burden (the development of super-bugs).

We are currently testing these biomarkers in a controlled clinical trial called the TRACE-COPD trial (Chraracterisation and targeted TReatment of ACute Exacerbations of Chronic Obstructive Pulmonary Disease), which is conducted in Wythenshawe and Salford Hospitals, led by Professor Jørgen Vestbo, the lead of the Respiratory Theme of the NIHR Manchester BRC. More specifically, we are testing whether the combination of procalcitonin and blood eosinophil count can indeed identify moderate or severe COPD exacerbations associated with bacterial infection or airway inflammation with eosinophils and can safely and effectively decrease and target the administration of antibiotics and/or steroids. In the well-studied population of this trial, we also plan to explore different molecular pathways of inflammation, aiming to identify differences among the previously described types of COPD exacerbations, as well as tests that could help in their diagnosis, predict their severity or distinguish other types of exacerbations, such as those caused by viruses.

This study which will run via Manchester Clinical Research Facility could revolutionise the assessment, management and outcomes of COPD exacerbations, improve patients’ health, quality of life and survival, reduce global antibiotic prescription rate and consequently, the burden of antibiotic resistance.