• Shahriyar Shahbazi Khamas, Yoni Van Dijk, Mahmoud I Abdel-Aziz, Anne H Neerincx, Maarten BlankestijnJelleJDepartment of Pulmonary Medicine and.Department of Paediatric Pulmonary Medicine, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.Amsterdam Institute for Infection and Immunity, Amsterd, VijverbergSusanne J HSJHDepartment of Pulmonary Medicine and.Department of Paediatric Pulmonary Medicine, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.Amsterdam Institute for Infection and Immunity, Amsterda, 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 Fleming, Maria 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-Hilse Maitland-van der Zee, and SysPharmPediA and U-BIOPRED Consortia.
• Department of Pulmonary Medicine and.
• Am. J. Respir. Crit. Care Med. 2024 Nov 1; 210 (9): 109111001091-1100.

AbstractRationale: 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.

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