Improving outcomes in interstitial lung disease through the application of bioinformatics and systems biology
File(s)
Author(s)
Sivananthan, Arunon
Type
Thesis
Abstract
Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are two distinct respiratory diseases whose features including pathogenesis and progression are not fully understood. However, both clinicians utilise changes in serial pulmonary function measurements to gain an insight into disease severity and control. More accurate prediction of disease progression would be beneficial, particularly for IPF given the variability in its clinical course as an unknown factor at the time of diagnosis.
Home-based, real-time monitoring of disease progression by spirometry has provided an opportunity to optimise the delivery of treatment and reduce the length of clinical trials. Therefore, the potential to understand the mechanisms underlying disease progression and generate effective treatment has been improved. In light of this, the motivation for this project is to understand the mathematical features within daily pulmonary function time series generated by IPF patients. Hopefully, statistical models of pulmonary function time series would aid the identification of significant clinical events such as acute exacerbation.
The mathematical techniques used to identify potentially important features within pulmonary function time series involved the autocorrelation function, critical transitions and detrended fluctuation analysis (DFA). Temporal properties, such as the serial correlation, abrupt changes in trends and complexity, were assessed using time series from the PROFILE clinical trial and London COPD cohort.
Forced vital capacity (FVC) measurements were found to be correlated to the previous day’s reading which may inform the sampling rate of lung function during clinical trials. The presence of short-term memory within FVC time series will influence the management of missing data within clinical trials, particularly methods of imputation. Also, FVC time series’ exhibit long-term memory and adaptability supporting the role of FVC as a surrogate marker for IPF disease progression.
Home-based, real-time monitoring of disease progression by spirometry has provided an opportunity to optimise the delivery of treatment and reduce the length of clinical trials. Therefore, the potential to understand the mechanisms underlying disease progression and generate effective treatment has been improved. In light of this, the motivation for this project is to understand the mathematical features within daily pulmonary function time series generated by IPF patients. Hopefully, statistical models of pulmonary function time series would aid the identification of significant clinical events such as acute exacerbation.
The mathematical techniques used to identify potentially important features within pulmonary function time series involved the autocorrelation function, critical transitions and detrended fluctuation analysis (DFA). Temporal properties, such as the serial correlation, abrupt changes in trends and complexity, were assessed using time series from the PROFILE clinical trial and London COPD cohort.
Forced vital capacity (FVC) measurements were found to be correlated to the previous day’s reading which may inform the sampling rate of lung function during clinical trials. The presence of short-term memory within FVC time series will influence the management of missing data within clinical trials, particularly methods of imputation. Also, FVC time series’ exhibit long-term memory and adaptability supporting the role of FVC as a surrogate marker for IPF disease progression.
Version
Open Access
Date Issued
2019-11
Date Awarded
2020-10
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Byrne, Adam
Molyneaux, Philip
Maher, Toby
Donaldson, Gavin
Sponsor
British Lung Foundation
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Masters
Qualification Name
Master of Philosophy (MPhil)