TY - JOUR
T1 - Exhaled Volatile Organic Compounds for Asthma Control Classification in Children with Moderate to Severe Asthma
T2 - Results from the SysPharmPediA Study
AU - Shahbazi Khamas, Shahriyar
AU - Van Dijk, Yoni
AU - Abdel-Aziz, Mahmoud I
AU - Neerincx, Anne H
AU - Maarten Blankestijn, Jelle
AU - Vijverberg, Susanne J H
AU - Hashimoto, Simone
AU - Bush, Andrew
AU - Kraneveld, Aletta D
AU - Hedman, Anna M
AU - Toncheva, Antoaneta A
AU - Almqvist, Catarina
AU - Wolff, Christine
AU - Murray, Clare S
AU - Hedlin, Gunilla
AU - Roberts, Graham
AU - Adcock, Ian M
AU - Korta-Murua, Javier
AU - Bønnelykke, Klaus
AU - Fleming, Louise J
AU - Pino-Yanes, Maria
AU - Gorenjak, Mario
AU - Kabesch, Michael
AU - Sardón-Prado, Olaia
AU - Montuschi, Paolo
AU - Singer, Florian
AU - Elosegui, Paula Corcuera
AU - Fowler, Stephen J
AU - Brandstetter, Susanne
AU - Harner, Susanne
AU - Dahlén, Sven-Erik
AU - Potočnik, Uroš
AU - Frey, Urs
AU - van Aalderen, Wim
AU - Brinkman, Paul
AU - Maitland-van der Zee, Anke-Hilse
AU - SysPharmPediA and U-BIOPRED Consortia
PY - 2024/11/1
Y1 - 2024/11/1
N2 - 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.
AB - 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.
KW - asthma
KW - biomarkers
KW - breath tests
KW - gas chromatography-mass spectrometry
KW - volatile organic compounds
UR - https://www.scopus.com/pages/publications/85193934961
U2 - 10.1164/rccm.202312-2270OC
DO - 10.1164/rccm.202312-2270OC
M3 - Journal article
C2 - 38648186
SN - 1073-449X
VL - 210
SP - 1091
EP - 1100
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 9
ER -