Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe Asthma

The measurement of exhaled volatile organic compounds (VOCs) in exhaled breath (breathomics) represents an exciting biomarker matrix for airways disease, with early research indicating a sensitivity to airway inflammation. One of the key aspects to analytical validity for any clinical biomarker is a...

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Main Authors: Adnan Azim, Faisal I. Rezwan, Clair Barber, Matthew Harvey, Ramesh J. Kurukulaaratchy, John W. Holloway, Peter H. Howarth
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Journal of Personalized Medicine
Subjects:
Online Access:https://www.mdpi.com/2075-4426/12/10/1635
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author Adnan Azim
Faisal I. Rezwan
Clair Barber
Matthew Harvey
Ramesh J. Kurukulaaratchy
John W. Holloway
Peter H. Howarth
author_facet Adnan Azim
Faisal I. Rezwan
Clair Barber
Matthew Harvey
Ramesh J. Kurukulaaratchy
John W. Holloway
Peter H. Howarth
author_sort Adnan Azim
collection DOAJ
description The measurement of exhaled volatile organic compounds (VOCs) in exhaled breath (breathomics) represents an exciting biomarker matrix for airways disease, with early research indicating a sensitivity to airway inflammation. One of the key aspects to analytical validity for any clinical biomarker is an understanding of the short-term repeatability of measures. We collected exhaled breath samples on 5 consecutive days in 14 subjects with severe asthma who had undergone extensive clinical characterisation. Principal component analysis on VOC abundance across all breath samples revealed no variance due to the day of sampling. Samples from the same patients clustered together and there was some separation according to T2 inflammatory markers. The intra-subject and between-subject variability of each VOC was calculated across the 70 samples and identified 30.35% of VOCs to be erratic: variable between subjects but also variable in the same subject. Exclusion of these erratic VOCs from machine learning approaches revealed no apparent loss of structure to the underlying data or loss of relationship with salient clinical characteristics. Moreover, cluster evaluation by the silhouette coefficient indicates more distinct clustering. We are able to describe the short-term repeatability of breath samples in a severe asthma population and corroborate its sensitivity to airway inflammation. We also describe a novel variance-based feature selection tool that, when applied to larger clinical studies, could improve machine learning model predictions.
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spelling doaj.art-f1eac78313594a2088429a22b80797482023-11-24T00:49:36ZengMDPI AGJournal of Personalized Medicine2075-44262022-10-011210163510.3390/jpm12101635Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe AsthmaAdnan Azim0Faisal I. Rezwan1Clair Barber2Matthew Harvey3Ramesh J. Kurukulaaratchy4John W. Holloway5Peter H. Howarth6Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UKDepartment of Computer Science, Aberystwyth University, Aberystwyth SY23 3DB, UKClinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UKNIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UKClinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UKNIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UKClinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UKThe measurement of exhaled volatile organic compounds (VOCs) in exhaled breath (breathomics) represents an exciting biomarker matrix for airways disease, with early research indicating a sensitivity to airway inflammation. One of the key aspects to analytical validity for any clinical biomarker is an understanding of the short-term repeatability of measures. We collected exhaled breath samples on 5 consecutive days in 14 subjects with severe asthma who had undergone extensive clinical characterisation. Principal component analysis on VOC abundance across all breath samples revealed no variance due to the day of sampling. Samples from the same patients clustered together and there was some separation according to T2 inflammatory markers. The intra-subject and between-subject variability of each VOC was calculated across the 70 samples and identified 30.35% of VOCs to be erratic: variable between subjects but also variable in the same subject. Exclusion of these erratic VOCs from machine learning approaches revealed no apparent loss of structure to the underlying data or loss of relationship with salient clinical characteristics. Moreover, cluster evaluation by the silhouette coefficient indicates more distinct clustering. We are able to describe the short-term repeatability of breath samples in a severe asthma population and corroborate its sensitivity to airway inflammation. We also describe a novel variance-based feature selection tool that, when applied to larger clinical studies, could improve machine learning model predictions.https://www.mdpi.com/2075-4426/12/10/1635breathomicsVOCvolatile organic compoundsrepeatabilityasthmasevere asthma
spellingShingle Adnan Azim
Faisal I. Rezwan
Clair Barber
Matthew Harvey
Ramesh J. Kurukulaaratchy
John W. Holloway
Peter H. Howarth
Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe Asthma
Journal of Personalized Medicine
breathomics
VOC
volatile organic compounds
repeatability
asthma
severe asthma
title Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe Asthma
title_full Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe Asthma
title_fullStr Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe Asthma
title_full_unstemmed Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe Asthma
title_short Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe Asthma
title_sort measurement of exhaled volatile organic compounds as a biomarker for personalised medicine assessment of short term repeatability in severe asthma
topic breathomics
VOC
volatile organic compounds
repeatability
asthma
severe asthma
url https://www.mdpi.com/2075-4426/12/10/1635
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