Methodology and feasibility of randomised controlled trials evaluating precision medicine interventions for acute exacerbations of chronic obstructive pulmonary disease (COPD)

Student thesis: Phd


Chronic Obstructive Pulmonary Disease (COPD) is a burdensome, long-term lung disease, causing persistent respiratory symptoms and poor quality of life. It is frequent, affecting more than 10% of people aged over forty. Patients often experience exacerbations, which are symptom flare-ups causing poor health and are responsible for 1 in 8 hospital admissions. There are different types of exacerbations. Some are caused by bacteria (bugs) and should be treated with antibiotics. Other are caused by inflammation of the airways with eosinophils (which are specific cells of the immune system) and respond to oral steroids. And some are caused by viruses and require antiviral treatments. However, we do not have accurate tests to distinguish different types of 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 often antibiotics to treat infections. Therefore, both antibiotics and steroids are massively overused and can cause side effects, or the development of super-bugs. Moreover, exacerbations triggered by viruses are not treated properly. The aim of my work was to lay the groundwork for high-quality clinical trials that will test novel personalised treatments for COPD flare-ups. I set up a clinical trial to preliminary assess whether personalised treatments for flare-ups are safe. More importantly, I wanted to look for potential challenges that need to be looked at before setting up larger trials. This pilot trial has not been completed due to COVID-19 pandemic. However, we have already found and resolved several problems, to ensure both this and future trials will be completed successfully. I also looked at the measures (outcomes) that researchers use to test if new treatments work and whether they are safe. Trials should test outcomes that are important to patients, but this is not always the case. For this reason, I brought together a global team of experts and patients that agreed on the most critical outcomes to be tested in all future trials of COPD flare-ups treatment. To achieve that, we completed systematic reviews, interviews with patients, a two-stage online survey and two meetings with international representation. We involved patients, health professionals and researchers. The agreed outcomes are endorsed by four international respiratory societies. Finally, through a systematic review we found how frequently people with COPD and COPD flare-ups suffer from infections by different viruses. These findings will inform the design of trials of novel personalised treatments for flare ups.
Date of Award1 Aug 2022
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorJacky Smith (Supervisor) & Jorgen Vestbo (Supervisor)


  • Evidence Based Medicine
  • Core Outcome Sets
  • Clinical Trial Methods
  • COPD Exacerbations
  • COPD
  • Treatable Traits

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