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Am J Respir Crit Care Med. 2019 Apr 11. doi: 10.1164/rccm.201811-2210OC. [Epub ahead of print]

Exhaled Volatile Organic Compounds are Able to Discriminate between Neutrophilic and Eosinophilic Asthma.

Author information

1
University of Liege, Department of Respiratory Diseases, Liege, Belgium ; fschleich@chuliege.be.
2
University of Liege, Organic and Biological Analytical Chemistry Group, Liege, Belgium.
3
University of Liege, Organic and Biological Analytical Chemistry Group , Liege, Belgium.
4
University of Liege, Medical Genomics-BIO3, GIGA-R, Liege, Belgium.
5
Toxicology and Metabolism (NUTRIM), MUMC+, Department of Toxicology, school for Nutrition, Maastricht, Netherlands.
6
School for Nutrition, Toxicology and Metabolism (NUTRIM), MUMC+, Department of Toxicology, Maastiricht, Netherlands.
7
CHU de Liege - Hopital du Sart Tilman, 82316, Liege, Belgium.
8
University of Liege, Respiratory Medicine, Liège, Liège, Belgium.
9
University of Liege, Department of Respiratory Diseases, Liege, Belgium.
10
University Hospital Maastricht, Department of Respiratory Medicine, Maastricht, Netherlands.
11
University of Liege, Medical Genomics-BIO3, GIGA-R, Liège, Liège, Belgium.

Abstract

RATIONALE:

Analysis of exhaled breath for asthma phenotyping using endogenously generated volatile organic compounds (VOCs) offers the possibility of noninvasive diagnosis and therapeutic monitoring. Induced sputum is indeed not widely available and markers of neutrophilic asthma are still lacking.

METHODS:

We conducted a prospective study on 521 asthmatics recruited from the University Asthma Clinic of Liege. Patient underwent VOC measurement, fraction of exhaled nitric oxide (FeNO) spirometry, sputum induction and gave a blood sample. Asthmatics were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.

RESULTS:

In the discovery study, seven potential biomarkers were highlighted by GC-MS in a training cohort of 276 asthmatics. In the replication study (n=245), we confirmed 4 VOCs of interest to discriminate between asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC×GC-HRTOFMS). Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to the one of blood eosinophils and FeNO. Moreover the combination of FeNO, blood eosinophils and VOCs gave a very good prediction of eosinophilic asthma (AUROC: 0.9). For neutrophilic asthma, the combination of nonanal, 1-propanol and hexane had a classification performance similar to FeNO or blood eosinophils in eosinophilic asthma. Those compounds were found in higher levels in neutrophilic asthma.

CONCLUSION:

Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of asthmatics and provide surrogate markers for neutrophilic asthma.

KEYWORDS:

biomarker; inflammation; phenotype

PMID:
30973757
DOI:
10.1164/rccm.201811-2210OC

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