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Title: Abnormal recovery and recurrence of chronic obstructive pulmonary disease exacerbations
Author: Mackay, A. J.
ISNI:       0000 0004 8503 9341
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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This thesis examines chronic obstructive pulmonary disease (COPD) exacerbation recovery in depth. This is an important topic to study since prolonged recovery and recurrence are common, severe and poorly understood events. The methodology involved patient reported outcome (PRO) tools and objective cough monitoring to examine symptomatic changes during exacerbations, and also the measurement of systemic and airway biomarkers during COPD exacerbations to identify patients at risk of non-recovery and recurrence. Finally, this thesis also included a randomised placebocontrolled trial to investigate if Roflumilast can improve exacerbation recovery. This thesis showed that PROs provide reliable measurements of exacerbation severity. Furthermore, cough frequency increased acutely from baseline levels at exacerbation and fell during subsequent recovery. The biomarker work demonstrated that increased systemic inflammation at exacerbation onset predicts non-recovery and that faster resolution of neutrophilic inflammation is associated with shorter recovery. Roflumilast did not accelerate reduction of sputum neutrophils from exacerbation onset to 2 weeks post exacerbation, but did improve lung function recovery when given on top of standard therapy. This thesis demonstrates that PROs can be used in clinical practice to evaluate exacerbation recovery, and in trials of acute exacerbation therapies. It also provides evidence that targeting inflammation may improve recovery time. Future research should seek to define the use of Roflumilast as part of a personalised strategy that treats patients according to exacerbation phenotype.
Supervisor: Wedzicha, W. ; Donaldson, G. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available