Eosinophilic airway inflammation, VOC biomarkers, Severe asthma
Abstract :
[en] [en] RATIONALE: Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker-signature to predict sputum eosinophilia in asthma.
METHODS: VOCs emitted into the space above sputum samples (headspace) from severe asthmatics (n=36) were collected onto sorbent tubes and analysed using thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Elastic net regression identified stable VOCs associated with sputum eosinophilia ≥3% and generated a volatile biomarker signature. This VOC signature was validated in breath samples from: (I) acute asthmatics according to blood eosinophilia ≥0.3x109cells/L or sputum eosinophilia of ≥ 3% in the UK EMBER consortium (n=65) and U-BIOPRED-IMI consortium (n=42). Breath samples were collected onto sorbent tubes (EMBER) or Tedlar bags (U-BIOPRED) and analysed by gas-chromatography-mass spectrometry (GC×GC-MS -EMBER or GC-MS -U-BIOPRED).
MAIN RESULTS: The in vitro headspace identified 19 VOCs associated with sputum eosinophilia and the derived VOC signature yielded good diagnostic accuracy for sputum eosinophilia ≥ 3% in headspace (AUROC (95% CI) 0.90(0.80-0.99), p<0.0001), correlated inversely with sputum eosinophil % (rs= -0.71, p<0.0001) and outperformed FeNO (AUROC (95% CI) 0.61(0.35-0.86). Analysis of exhaled breath in replication cohorts yielded a VOC signature AUROC (95% CI) for acute asthma exacerbations of 0.89(0.76-1.0) (EMBER cohort) with sputum eosinophilia and 0.90(0.75-1.0) in U-BIOPRED - again outperforming FeNO in U-BIOPRED 0.62 (0.33-0.90).
CONCLUSIONS: We have discovered and provided early-stage clinical validation of a volatile biomarker signature associated with eosinophilic airway inflammation. Further work is needed to translate our discovery using point of care clinical sensors.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Peltrini, Rosa; University of Leicester, Department of Respiratory Sciences, Leicester, United Kingdom of Great Britain and Northern Ireland
Cordell, Rebecca L; University of Leicester, Department of Chemistry , LE1 7RH, Leicester, United Kingdom of Great Britain and Northern Ireland
Wilde, Michael; University of Leicester, Department of Chemistry, LE1 7RH, Leicester, United Kingdom of Great Britain and Northern Ireland ; University of Plymouth, School of Geography, Earth and Environmental Sciences, Plymouth, United Kingdom of Great Britain and Northern Ireland
Abuhelal, Shahd; Imperial College London, National Heart and Lung Institute (NHLI), London, United Kingdom of Great Britain and Northern Ireland
Quek, Eleanor; Imperial College London, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
Zounemat-Kermani, Nazanin; Imperial College London, National Heart and Lung Institute (NHLI), London, United Kingdom of Great Britain and Northern Ireland
Ibrahim, Wadah; Glenfield Hospital, Institute for Lung Health, NIHR Leicester Biomedical Research Centre (Respiratory theme), Leicester, United Kingdom of Great Britain and Northern Ireland
Richardson, Matthew; University of Leicester, Department of Respiratory Sciences , Leicester, United Kingdom of Great Britain and Northern Ireland
Brinkman, Paul; Amsterdam UMC - Locatie AMC, Department of Respiratory Medicine, Amsterdam, North Holland, Netherlands
Aung, Hnin; University of Leicester, Department of Respiratory Sciences, Leicester, United Kingdom of Great Britain and Northern Ireland
Greening, Neil; Universtiy of Leicester, Department of Respiratory Sciences, Leicester, United Kingdom of Great Britain and Northern Ireland
Dahlen, Sven Erik; Karolinska Institute, Experimental Asthma and Allergy Research, Institute of Environmental Medicine, Stockholm, Sweden
Djukanovic, Ratko; University of Southampton, Clinical & Experimental Sciences, Southampton, United Kingdom of Great Britain and Northern Ireland
Adcock, Ian M ; Imperial College London, National heart and Lung institute (NHLI), London, United Kingdom of Great Britain and Northern Ireland
Brightling, Christopher; University of Leicester, Department of Respiratory Sciences, Leicester, United Kingdom of Great Britain and Northern Ireland
Monks, Paul; University of Leicester, School of Chemistry, Leicester, United Kingdom of Great Britain and Northern Ireland
Siddiqui, Salman; Imperial College London, National Heart and Lung Institute (NHLI), NIHR Imperial Biomedical Research Centre, London, United Kingdom of Great Britain and Northern Ireland ; University of Leicester, Department of Respiratory Sciences, Leicester, United Kingdom of Great Britain and Northern Ireland, s.siddiqui@imperial.ac.uk
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