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 - 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 - Corcuera-Elosegui, Paula
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 H
PY - 2024/4/22
Y1 - 2024/4/22
N2 - 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.
AB - 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.
U2 - 10.1164/rccm.202312-2270OC
DO - 10.1164/rccm.202312-2270OC
M3 - Article
C2 - 38648186
SN - 1073-449X
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
ER -