Mathematical modelling of long-term progression of atopic dermatitis
File(s)
Author(s)
Day, Harley
Type
Thesis
Abstract
The skin is the largest organ of the human body, and performs a vital defensive and physiological role, protecting the delicate tissues beneath from pathogens and physical damage while preventing water loss and regulating body temperature. Many of these protective functions are performed by the epidermis, a paper-thin layer of cells rich in structural proteins and lipids which produce antimicrobial peptides and plays host to cells of the immune system. Failure of this epidermal layer of the skin to maintain a competent barrier against pathogens can trigger the activation of allergic immune responses, causing the most common form of skin disease, atopic dermatitis (AD).
While mild-to-moderate AD can usually be well controlled by emollient and corticosteroid therapies, some AD patients go on to develop a more treatment-resistant form of chronic AD. The pathophysiological mechanisms of chronic AD are poorly understood, making development of new therapies and management of chronic AD difficult.
In this thesis, we develop a mechanistic mathematical model of chronic AD with the aim of elucidating how the complicated disease dynamics of chronic AD emerge as the result of dysregulated interactions between the barrier and immune system. We show how different genotypes can lead to different disease dynamics and propose how various therapies might affect these dynamics.
The model we develop is structured as a hybrid dynamical system, consisting of both continuous-valued and discrete-valued components which interact to produce counterintuitive dynamical properties. We develop a series of novel methods designed to elucidate the range of dynamics available in our model. Finally, we investigate how the methods we develop here can be applied to hybrid dynamical systems more broadly.
While mild-to-moderate AD can usually be well controlled by emollient and corticosteroid therapies, some AD patients go on to develop a more treatment-resistant form of chronic AD. The pathophysiological mechanisms of chronic AD are poorly understood, making development of new therapies and management of chronic AD difficult.
In this thesis, we develop a mechanistic mathematical model of chronic AD with the aim of elucidating how the complicated disease dynamics of chronic AD emerge as the result of dysregulated interactions between the barrier and immune system. We show how different genotypes can lead to different disease dynamics and propose how various therapies might affect these dynamics.
The model we develop is structured as a hybrid dynamical system, consisting of both continuous-valued and discrete-valued components which interact to produce counterintuitive dynamical properties. We develop a series of novel methods designed to elucidate the range of dynamics available in our model. Finally, we investigate how the methods we develop here can be applied to hybrid dynamical systems more broadly.
Version
Open Access
Date Issued
2023-09-27
Date Awarded
2024-03-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Tanaka, Reiko
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)