Biomarkers to Guide the use of Antibiotics for Acute Exacerbations of COPD (AECOPD)

A Systematic Review and Meta-Analysis

George Hoult; David Gillespie; Tom M. A. Wilkinson; Mike Thomas; Nick A. Francis


BMC Pulm Med. 2022;22(194) 

In This Article


Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide and incidence is predicted to increase each year until at least 2030.[1] Exacerbations are defined as "acute worsening of respiratory symptoms that result in additional therapy" and carry with them significant risk of morbidity and mortality, as well as worsening disease prognosis.[2] The GOLD international guideline recommends use of antibiotics for acute exacerbations of COPD (AECOPD) in patients with increased sputum purulence who have one or both of increased dyspnoea and increased sputum volume, as well as patients that require mechanical ventilation.[3] U.K. NICE guidance advises prescribers to consider the severity of symptoms, particularly sputum colour changes and increases in volume or thickness, whether they may need to go to hospital, previous exacerbation and hospitalisation history, and the risk of developing complications, previous sputum culture results, and the risk of antimicrobial resistance when considering whether or not to prescribe antibiotics for patients with AECOPD.[4] As a result, although less than 50% of exacerbations involve bacterial infection, around three quarters of those managed in primary care, and nearly all of those managed in hospital, are treated with antibiotics.[5–7] Inappropriate use of antibiotics is the key driver of antimicrobial resistance, a major public health threat, and can also lead to adverse effects, damaging changes in the microbiome, wasted resources, and distraction from more appropriate therapy. There is therefore an urgent need to develop approaches for better diagnosing bacterial infection in a timely fashion. One such approach is the use of biomarkers.

Biomarkers are defined as "A defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes or responses to an exposure or intervention".[8] In the context of AECOPD, we are referring primarily to the measurement of molecules that are either directly from a pathogen (e.g. nucleic acid) or result from the host's response to the pathogen, and can be measured from blood or respiratory secretions. Host responses could be either broad inflammatory markers (such as C-reactive protein) or more specific immune or inflammatory markers. New molecular technologies have improved our ability to detect and quantify biomarkers and led to a proliferation of studies on their diagnostic properties.