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Investigation of the Utility of Optical Spectroscopy for Management of Chronic Respiratory Disease through Investigation of Sputum Mucin Glycosylation Patterns / Charles D. Brilliant

DOI (Published version): 10.23889/Suthesis.50576

Abstract

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...

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Published: Swansea 2019
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa50576
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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. 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spelling 2022-09-27T16:24:31.3695176 v2 50576 2019-05-30 Investigation of the Utility of Optical Spectroscopy for Management of Chronic Respiratory Disease through Investigation of Sputum Mucin Glycosylation Patterns 2019-05-30 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. E-Thesis Swansea Fourier-transform infrared spectroscopy, FTIR, vibrational spectroscopy, respiratory disease, lung cancer, cystic fibrosis, CF, COPD, chronic obstructive pulmonary disease, mucins, mucus, glycans, glycosylation, early diagnosis, exacerbation, novel therap 31 12 2019 2019-12-31 10.23889/Suthesis.50576 A selection of third party content is redacted or is partially redacted from this thesis. COLLEGE NANME COLLEGE CODE Swansea University Doctoral Ph.D Health and Care Research Wales 2022-09-27T16:24:31.3695176 2019-05-30T15:29:13.6835527 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Charles D. Brilliant 1 0050576-30052019162347.pdf Brilliant_Charles_D_PhD_Thesis_Final_Embargoed_01.05.2024_Redacted.pdf 2019-05-30T16:23:47.4030000 Output 17469730 application/pdf Redacted version - open access true 2022-05-21T00:00:00.0000000 true
title Investigation of the Utility of Optical Spectroscopy for Management of Chronic Respiratory Disease through Investigation of Sputum Mucin Glycosylation Patterns
spellingShingle Investigation of the Utility of Optical Spectroscopy for Management of Chronic Respiratory Disease through Investigation of Sputum Mucin Glycosylation Patterns
,
title_short Investigation of the Utility of Optical Spectroscopy for Management of Chronic Respiratory Disease through Investigation of Sputum Mucin Glycosylation Patterns
title_full Investigation of the Utility of Optical Spectroscopy for Management of Chronic Respiratory Disease through Investigation of Sputum Mucin Glycosylation Patterns
title_fullStr Investigation of the Utility of Optical Spectroscopy for Management of Chronic Respiratory Disease through Investigation of Sputum Mucin Glycosylation Patterns
title_full_unstemmed Investigation of the Utility of Optical Spectroscopy for Management of Chronic Respiratory Disease through Investigation of Sputum Mucin Glycosylation Patterns
title_sort Investigation of the Utility of Optical Spectroscopy for Management of Chronic Respiratory Disease through Investigation of Sputum Mucin Glycosylation Patterns
author ,
author2 Charles D. Brilliant
format E-Thesis
publishDate 2019
institution Swansea University
doi_str_mv 10.23889/Suthesis.50576
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description 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.
published_date 2019-12-31T04:02:04Z
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score 11.028886

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