Increased breath naphthalene in children with asthma and wheeze of the All Age Asthma Cohort (ALLIANCE)

Abstract

Background
Exhaled breath contains numerous volatile organic compounds (VOCs) known to be related to lung disease like asthma. Its collection is non-invasive, simple to perform and therefore an attractive method for the use even in young children. We analysed breath in children of the multicenter All Age Asthma Cohort (ALLIANCE) to evaluate if “breathomics” have the potential to phenotype patients with asthma and wheeze, and to identify extrinsic risk factors for underlying disease mechanisms.
Methods
A breath sample was collected from 142 children (asthma: 51, pre-school wheezers: 55, healthy controls: 36) and analysed using gas chromatography–mass spectrometry (GC/MS). Children were diagnosed according to GINA guidelines and comprehensively examined each year over up to seven years. Forty children repeated the breath collection after 24 or 48 months. 
Results
Most breath VOCs differing between groups reflect the exposome of the children. We observed lower levels of lifestyle-related VOCs and higher levels of the environmental pollutants, especially naphthalene, in children with asthma or wheeze. Naphthalene was also higher in symptomatic patients and in wheezers with recent inhaled corticosteroid use. No relationships with lung function or TH2 inflammation were detected.
Conclusion
Increased levels of naphthalene in asthmatics and wheezers and the relationship to disease severity could indicate a role of environmental or indoor air pollution for the development or progress of asthma. Breath VOCs might help to elucidate the role of the exposome for the development of asthma.
The study was registered at ClinicalTrials.gov (NCT02496468).


Progress and challenges of developing volatile metabolites from exhaled breath as a biomarker platform

“…The prevalence of hydrocarbons and carbonyls in this study strongly associates lipid peroxidation as a major origin of characteristic VOCs in the breath of those with respiratory conditions. Chronic inflammation generates oxidative stress, resulting in the generation of reactive oxygen species that can react with unsaturated fatty acids in the cell (lipid peroxidation), and the subsequent release of characteristic volatile compounds such as alkanes, aldehydes, hydrocarbons, and carbonyls (Caldeira et al, 2012 ; Ibrahim et al, 2022 ; Monedeiro et al, 2021 ; Ratcliffe et al, 2020 ; Shahrokny et al, 2023 ; Sharma et al, 2021 ; van Vliet et al, 2017 ; Wijsman et al, 2024 ).…”