Abstract
People suffering with airway diseases such as Chronic Obstructive Pulmonary Disease and bronchiectasis can find that their lives are overtaken by the disease. They often struggle to cope with day-to-day activities, but they particularly struggle at the point of exacerbation – a temporary worsening of symptoms which often requires additional treatment. This may warrant a course of antibiotics or even admission to hospital for observation and treatment. It is thought that early treatment of these exacerbations may curtail the worsening of symptoms before they become severe and ease the overall course of the deterioration in pulmonary function. The current standard of care is a self-management plan. This tailored document gives the person features to look out for such as worsening breathlessness, cough or increased sputum production for example, and when to start a course of additional treatment such as a course of antibiotics at home using a “rescue pack”. This work aims to find out if there is a way to detect the onset of exacerbations earlier and so help to partially relieve these people of some of their worst symptoms.This thesis comprises a multi-modal examination of a longitudinal study of people with Chronic Obstructive Pulmonary Disease and/or bronchiectasis, frequent exacerbations and colonisation with Pseudomonas aeruginosa or Haemophilus influenzae, two bacteria which can imply more severe disease. Firstly, the microbiological environment of the exacerbations is examined by multiplex polymerase chain reaction to determine whether the participants symptoms are worse due to a new infection or their existing disease. This demonstrates that over half of exacerbations did not demonstrate any change in polymerase chain reaction detectable airway microbiota suggesting that detection of viruses and bacteria is not likely to help with prediction of an exacerbation in people who are known to be colonised. Secondly, the participants “vital signs” and symptoms are examined to map the time-course of the flare of disease and whether there is an opportunity to intervene earlier based on these measures. Symptoms are found to be more predictive of an exacerbation than vital signs but neither symptoms nor vital signs are sufficiently predictive in this population to base treatment decisions on the results. Finally urinary biomarkers are examined to determine if selected non-invasive biomarkers could be used to detect an exacerbation. This demonstrates significant reductions in urinary C-X-C chemokine ligand 10 and interleukin 6 at exacerbation, but this was not consistent and concentrations were higher at exacerbation for some participants.
Overall, these data show the heterogeneity of exacerbations of airway disease and of those that suffer from them. A deterioration in symptoms showed the most promise in predicting an exacerbation, but the difference between people in symptom severity was much greater than the change prior to an exacerbation demonstrating that guidance and predictive models need to be personalised. Urinary biomarkers were detectable but changes at exacerbation were inconsistent.
Date of Award | 16 Oct 2024 |
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Original language | English |
Awarding Institution |
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Supervisor | Janis Kay Shute (Supervisor) & Anoop Chauhan (Supervisor) |