Exhaled Volatile Organic Compounds for Asthma Control Classification in Children with Moderate to Severe Asthma: Results from the SysPharmPediA Study

Shahriyar Shahbazi Khamas, Yoni Van Dijk, Mahmoud I Abdel-Aziz, Anne H Neerincx, Jelle Blankestijn, Susanne J H Vijverberg, Simone Hashimoto, Andrew Bush, Aletta D Kraneveld, Anna M Hedman, Antoaneta A Toncheva, Catarina Almqvist, Christine Wolff, Clare S Murray, Gunilla Hedlin, Graham Roberts, Ian M Adcock, Javier Korta-Murua, Klaus Bønnelykke, Louise J FlemingMaria Pino-Yanes, Mario Gorenjak, Michael Kabesch, Olaia Sardón-Prado, Paolo Montuschi, Florian Singer, Paula Corcuera-Elosegui, Stephen J Fowler, Susanne Brandstetter, Susanne Harner, Sven-Erik Dahlén, Uroš Potočnik, Urs Frey, Wim van Aalderen, Paul Brinkman, Anke H Maitland-van der Zee

Research output: Contribution to journalArticleAcademicpeer-review


RATIONALE: Early identification of children with poorly controlled asthma is imperative for optimizing treatment strategies. The analysis of exhaled volatile organic compounds (VOCs) is an emerging approach to identify prognostic and diagnostic biomarkers in pediatric asthma.

OBJECTIVES: To assess the accuracy of gas chromatography-mass spectrometry based exhaled metabolite analysis to differentiate between controlled and uncontrolled pediatric asthma.

METHODS: This study encompassed a discovery (SysPharmPediA) and validation phase (U-BIOPRED, PANDA). Firstly, exhaled VOCs that discriminated asthma control levels were identified. Subsequently, outcomes were validated in two independent cohorts. Patients were classified as controlled or uncontrolled, based on asthma control test scores and number of severe attacks in the past year. Additionally, potential of VOCs in predicting two or more future severe asthma attacks in SysPharmPediA was evaluated.

MEASUREMENTS AND MAIN RESULTS: Complete data were available for 196 children (SysPharmPediA=100, U-BIOPRED=49, PANDA=47). In SysPharmPediA, after randomly splitting the population into training (n=51) and test sets (n=49), three compounds (acetophenone, ethylbenzene, and styrene) distinguished between uncontrolled and controlled asthmatics. The area under the receiver operating characteristic curve (AUROCC) for training and test sets were respectively: 0.83 (95% CI: 0.65-1.00) and 0.77 (95% CI: 0.58-0.96). Combinations of these VOCs resulted in AUROCCs of 0.74 ±0.06 (UBIOPRED) and 0.68 ±0.05 (PANDA). Attacks prediction tests, resulted in AUROCCs of 0.71 (95% CI 0.51-0.91) and 0.71 (95% CI 0.52-0.90) for training and test sets.

CONCLUSIONS: Exhaled metabolites analysis might enable asthma control classification in children. This should stimulate further development of exhaled metabolites-based point-of-care tests in asthma.

Original languageEnglish
JournalAmerican journal of respiratory and critical care medicine
Publication statusE-pub ahead of print - 22 Apr 2024
Externally publishedYes

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