BibTex format
@article{Peltrini:2024:10.1164/rccm.202310-1759OC,
author = {Peltrini, R and Cordell, RL and Wilde, M and Abuhelal, S and Quek, E and Zounemat-Kermani, N and Ibrahim, W and Richardson, M and Brinkman, P and Schleich, F and Stefanuto, P-H and Aung, H and Greening, N and Dahlen, SE and Djukanovic, R and Adcock, IM and Brightling, C and Monks, P and Siddiqui, S},
doi = {10.1164/rccm.202310-1759OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {1101--1112},
title = {Discovery and validation of a volatile signature of eosinophilic airway inflammation in asthma},
url = {http://dx.doi.org/10.1164/rccm.202310-1759OC},
volume = {210},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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.
AU - Peltrini,R
AU - Cordell,RL
AU - Wilde,M
AU - Abuhelal,S
AU - Quek,E
AU - Zounemat-Kermani,N
AU - Ibrahim,W
AU - Richardson,M
AU - Brinkman,P
AU - Schleich,F
AU - Stefanuto,P-H
AU - Aung,H
AU - Greening,N
AU - Dahlen,SE
AU - Djukanovic,R
AU - Adcock,IM
AU - Brightling,C
AU - Monks,P
AU - Siddiqui,S
DO - 10.1164/rccm.202310-1759OC
EP - 1112
PY - 2024///
SN - 1073-449X
SP - 1101
TI - Discovery and validation of a volatile signature of eosinophilic airway inflammation in asthma
T2 - American Journal of Respiratory and Critical Care Medicine
UR - http://dx.doi.org/10.1164/rccm.202310-1759OC
UR - https://www.ncbi.nlm.nih.gov/pubmed/38820123
UR - https://www.atsjournals.org/doi/10.1164/rccm.202310-1759OC
VL - 210
ER -