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. 2024 Nov 1;210(9):1091-1100.
doi: 10.1164/rccm.202312-2270OC.

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

Shahriyar Shahbazi Khamas  1   2   3   4 , Yoni Van Dijk  1   2   3   4 , Mahmoud I Abdel-Aziz  1   2   3   4 , Anne H Neerincx  1   2   3   4 , Jelle Maarten Blankestijn  1   2   3   4 , Susanne J H Vijverberg  1   2   3   4 , Simone Hashimoto  1   2   3   4 , Andrew Bush  5   6 , Aletta D Kraneveld  7 , Anna M Hedman  8 , Antoaneta A Toncheva  9 , Catarina Almqvist  8   10 , Christine Wolff  11 , Clare S Murray  12   13 , Gunilla Hedlin  14   15 , Graham Roberts  16 , Ian M Adcock  5   6 , Javier Korta-Murua  17 , Klaus Bønnelykke  18 , Louise J Fleming  5   6 , Maria Pino-Yanes  19   20   21 , Mario Gorenjak  22 , Michael Kabesch  9   11 , Olaia Sardón-Prado  17   23 , Paolo Montuschi  24 , Florian Singer  25   26 , Paula Corcuera Elosegui  17 , Stephen J Fowler  12   13 , Susanne Brandstetter  11 , Susanne Harner  9 , Sven-Erik Dahlén  27 , Uroš Potočnik  22   28   29 , Urs Frey  30 , Wim van Aalderen  4 , Paul Brinkman  1   2   3   4 , Anke-Hilse Maitland-van der Zee  1   2   3   4 ; SysPharmPediA and U-BIOPRED Consortia
Collaborators, Affiliations

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

Shahriyar Shahbazi Khamas et al. Am J Respir Crit Care Med. .

Abstract

Rationale: The 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 discovery (SysPharmPediA [Systems Pharmacology Approach to Uncontrolled Paediatric Asthma]) and validation (U-BIOPRED [Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes] and PANDA [Paediatric-Asthma-Non-Invasive-Diagnostic-Approaches]) phases. First, exhaled VOCs that discriminated degrees of asthma control were identified. Subsequently, outcomes were validated in two independent cohorts. Patients were classified as controlled or uncontrolled on the basis of asthma control test scores and the number of severe attacks in the past year. In addition, the potential of VOCs to predict two or more future severe asthma attacks in SysPharmPediA was evaluated. Measurements and Main Results: Complete data were available for 196 children (SysPharmPediA, n = 100; U-BIOPRED, n = 49; PANDA, n = 47). In SysPharmPediA, after randomly splitting the population into training (n = 51) and test (n = 49) sets, three compounds (acetophenone, ethylbenzene, and styrene) distinguished between patients with uncontrolled and controlled asthma. The areas under the receiver operating characteristic curves (AUROCCs) for training and test sets were, respectively, 0.83 (95% confidence interval [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 (U-BIOPRED) and 0.68 ± 0.05 (PANDA). Attack prediction tests resulted in AUROCCs of 0.71 (95% CI, 0.51-0.91) and 0.71 (95% CI, 0.52-0.90) for the training and test sets. Conclusions: Exhaled metabolite analysis might enable asthma control classification in children. This should stimulate the further development of exhaled metabolite-based point-of-care tests in asthma.

Keywords: asthma; biomarkers; breath tests; gas chromatography–mass spectrometry; volatile organic compounds.

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