Re-defining exacerbations of chronic obstructive pulmonary disease and developing tools to characterise heterogeneity and treatment response

Halner, A

Thesis

Re-defining exacerbations of chronic obstructive pulmonary disease and developing tools to characterise heterogeneity and treatment response

Alternative title:: Re-defining exacerbations of chronic obstructive pulmonary disease and developing tools to characterise heterogeneity and treatment response

Abstract:: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Progressive in nature, COPD is punctuated by acute periods of worsening termed ‘exacerbations’, a cause of morbidity and mortality. Exacerbations are heterogenous with respect to symptoms and inflammatory biology.

In this thesis, mathematical methods were researched for their appropriateness to characterise COPD heterogeneity and predict treatment response. Algorithms were developed to predict treatment outcome for a cohort of hospitalised patients with airways disease exacerbations. In a second patient cohort, cluster analysis was performed on longitudinal measurements at 'stable state’ and ‘exacerbation’ in order to define objective ‘states’ of COPD based on symptoms and inflammatory biology. Objective states included a low overall symptom burden state and crisis states with elevated symptoms with or without particular inflammation. Objective states were compared to conventional ‘stable state’ and ‘exacerbation’ definitions and found to better correspond to distinct patterns of symptoms and inflammation. Algorithms were trained and tested to identify to which objective state any given measurement of symptoms and inflammation from a patient belongs at a given point in time. Different treatment response trajectories or ‘trajectotypes’ of symptoms and inflammation were characterised for crisis states between the time of treatment and follow-up measurements. Trajectotypes included symptom resolution with or without different patterns of inflammatory resolution, as well as a trajectotype of no change between treatment and follow-up. Individualised symptom shape profile trajectories post-treatment were found from daily time series of self-reported symptom scores.

This thesis provides a new definition of COPD states as an alternative to ‘stable state’ and ‘exacerbation’ definitions. Together with the characterisation of distinct treatment response trajectories based on symptom and inflammatory resolution, the findings of this thesis set the stage for future clinical studies evaluating enhanced personalisation of treatment allocation and monitoring for patients with COPD.

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APA Style

Halner, A. (2022). Re-defining exacerbations of chronic obstructive pulmonary disease and developing tools to characterise heterogeneity and treatment response [PhD thesis]. University of Oxford.

MLA Style

Halner, A. Re-Defining Exacerbations of Chronic Obstructive Pulmonary Disease and Developing Tools to Characterise Heterogeneity and Treatment Response. 2022. University of Oxford, PhD thesis.

Chicago Style

Halner, A. 2022. “Re-Defining Exacerbations of Chronic Obstructive Pulmonary Disease and Developing Tools to Characterise Heterogeneity and Treatment Response.” PhD thesis, University of Oxford.
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