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Title: Investigation of the utility of optical spectroscopy for management of chronic respiratory disease through investigation of sputum mucin glycosylation patterns
Author: Brilliant, Charles D.
ISNI:       0000 0004 7967 4517
Awarding Body: Swansea University
Current Institution: Swansea University
Date of Award: 2019
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Chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), lung cancer and cystic fibrosis (CF) are leading causes of disease and death in the UK. These diseases are difficult to monitor and diagnose in an efficient and timely manner. In this work, Fourier-transform infrared spectroscopy (FTIR) was used to investigate sputum samples from lung cancer, COPD and CF patients for specific IR-spectral markers which could be utilised for the diagnosis and management of these conditions. It is proposed that spectral changes correspond to structural changes to sputum mucins, which could be biomarkers for COPD progression and exacerbation, for lung cancer diagnosis, and for CF patient monitoring. In this study, sputum samples from COPD patients were obtained for FTIR analysis to generate a spectral library for use in creation of a generalised predictive model for COPD exacerbation. It was found that COPD exacerbations are a highly complex and heterogeneous condition, which made the generation of a generalised predictive model for exacerbation problematic. One model developed in this work demonstrated a capability to determine exacerbation from COPD baseline samples with 80% sensitivity and 48% specificity. Small correlations were found between peak positions and absorbance intensities around wavenumbers associated with mucin glycoprotein structural change, and physiological factors, such as smoking status or lung function. FTIR spectroscopy was shown to have a very high power for distinguishing lung cancer sputum samples from non-cancer respiratory disease sputum samples, using a simple protocol with no sample pre-processing and linear regression modelling. A series of diagnostic algorithms were developed and were shown to have a greater than 90% sensitivity and specificity for detecting lung cancer from raw sputum. FTIR was also successfully utilised in the monitoring of CF patient sputum samples for the presence of a novel inhaled therapeutic, OligoG, during and after treatment. It was found that FTIR spectroscopy can readily detect very low concentrations of OligoG in sputum with no sample processing or targeting of the therapeutic necessary. In conclusion, FTIR was shown to be a powerful tool for analysis of raw sputum, capable of providing high-quality molecular structural information pertaining to the mucin glycoproteins, and proposed changes to these structures. Using this information, it is possible to distinguish lung cancer sputum from other respiratory disease sputum, and monitor the levels of a novel therapeutic in CF patient lungs. Associations were made between FTIR spectral features and physiological factors of COPD patients, however further work is needed to fully evaluate if COPD exacerbation can be predicted using this method.
Supervisor: Lewis, Paul D. ; Morgan, Claire. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral