Discovery and validation of a volatile signature of eosinophilic airway inflammation in asthma
Brightling, Christopher Greening, Neil Ibrahim, Wadah Siddiqui, Salman
Brightling, Christopher
Greening, Neil
Ibrahim, Wadah
Siddiqui, Salman
Abstract
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.
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Date
2024-05-31
Type
Article
Subject
Eosinophilic airway inflammation, VOC biomarkers, Severe asthma
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Citation
Peltrini, R., Cordell, R. L., Wilde, M., Abuhelal, S., Quek, E., Zounemat-Kermani, N., Ibrahim, W., Richardson, M., Brinkman, P., Schleich, F., Stefanuto, P. H., Aung, H., Greening, N., Dahlen, S. E., Djukanovic, R., Adcock, I. M., Brightling, C., Monks, P., & Siddiqui, S. (2024). Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma. American journal of respiratory and critical care medicine, 10.1164/rccm.202310-1759OC. Advance online publication. https://doi.org/10.1164/rccm.202310-1759OC