Bifurcation analysis of a mathematical model of atopic dermatitis to determine patient-specific effects of treatments on dynamic phenotypes
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Author(s)
Tanaka, Gouhei
Dominguez-Huttinger, Elisa
Christodoulides, Panayiotis
Kazuyuki, Aihara
Tanaka, RJ
Type
Journal Article
Abstract
Atopic dermatitis (AD) is a common inflammatory skin disease, whose incidence is currently increasing worldwide. AD has a complex etiology, involving genetic, environmental, immunological, and epidermal factors, and
its pathogenic mechanisms have not yet been fully elucidated. Identification
of AD risk factors and systematic understanding of their interactions are
required for exploring effective prevention and treatment strategies for AD.
We recently developed a mathematical model for AD pathogenesis to clarify
mechanisms underlying AD onset and progression. This model describes a
dynamic interplay between skin barrier, immune regulation, and environmental stress, and reproduced four types of dynamic behaviour typically observed in AD patients in response to environmental triggers. Here, we analyse bifurcations of the model to identify mathematical conditions for the system to demonstrate transitions between different types of dynamic behaviour that reflect respective severity of AD symptoms. By mathematically modelling effects of topical application of antibiotics, emollients, corticosteroids, and their combinations with different application schedules and doses, bifurcation analysis allows us to mathematically evaluate effects of the treatments on improving AD symptoms in terms of the patients' dynamic behaviour. The mathematical method developed in this study can be used to explore and improve patient-specific personalised treatment strategies to control AD symptoms.
its pathogenic mechanisms have not yet been fully elucidated. Identification
of AD risk factors and systematic understanding of their interactions are
required for exploring effective prevention and treatment strategies for AD.
We recently developed a mathematical model for AD pathogenesis to clarify
mechanisms underlying AD onset and progression. This model describes a
dynamic interplay between skin barrier, immune regulation, and environmental stress, and reproduced four types of dynamic behaviour typically observed in AD patients in response to environmental triggers. Here, we analyse bifurcations of the model to identify mathematical conditions for the system to demonstrate transitions between different types of dynamic behaviour that reflect respective severity of AD symptoms. By mathematically modelling effects of topical application of antibiotics, emollients, corticosteroids, and their combinations with different application schedules and doses, bifurcation analysis allows us to mathematically evaluate effects of the treatments on improving AD symptoms in terms of the patients' dynamic behaviour. The mathematical method developed in this study can be used to explore and improve patient-specific personalised treatment strategies to control AD symptoms.
Date Issued
2018-07-07
Date Acceptance
2018-04-02
Citation
Journal of Theoretical Biology, 2018, 448, pp.66-79
ISSN
0022-5193
Publisher
Elsevier
Start Page
66
End Page
79
Journal / Book Title
Journal of Theoretical Biology
Volume
448
Copyright Statement
© 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license. (http://creativecommons.org/licenses/by/4.0/ )
License URL
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Grant Number
EP/G007446/1
Subjects
Hybrid dynamical systems
bifurcations
patient stratification
personalised treatment strategies
systems medicine
Publication Status
Published
Date Publish Online
2018-04-03