Assessing asthma-specific breath markers in preschool children using remote breath collection

ABSTRACT
Asthma is the most common chronic respiratory disease in children. However, dis-tinguishing asthma from other respiratory complaints in preschool age remains a diagnostic challenge. Secondary electrospray ionization high resolution mass spec-trometry (SESI-HRMS) together with a remote breath sample collecting method is a promising tool to overcome this diagnostic problem. This study investigated whether previously identified asthma-specific volatile organic compounds (VOCs) can be reidentified in preschool children by SESI-HRMS using an offline breath collection device.
A total of 30 patients presenting with chronic respiratory symptoms (CRS) and referred for the investigation of preschool asthma as well as 32 healthy controls between 3 and 6 years of age were recruited from the outpatient clinic at the University Children’s Hospital in Zurich, Switzerland. Participants were instructed to exhale into an offline breath collection device entailing a Nalophan bag. Breath samples were transferred to SESI-HRMS in a heated box at body temperature.
Samples were pumped into SESI-HRMS using a pressurized box. Detection of previously identified asthma-specific markers (mass-to-charge ratio (m/z) tolerance of 0.002 Da) and statistical analysis were performed. Of 375 previously identified, asthma-specific m/z features, 125 were detected again in preschool children with the remote breath collection method. 16 detected m/z features showed statistically significant differences between patients with CRS and healthy controls (Wilcoxon rank-sum test, adjusted p-value <0.05). Eight of those 16 significant m/z features had been identified chemically as representatives of monosaccharide and fatty acid metabolism, lysine degradation and aldehydes in a previous study. Predictive performance of confirmed markers for distinguishing patients with CRS from healthy patients, using random forest algorithm in a repeated cross-validation, resulted in an AUC of 0.77 (95% CI: 0.60-0.93).
This is the first study to successfully reidentify asthma-specific VOCs in preschool children by SESI-HRMS using a breath collection device that entails Nalophan. Despite loss of m/z features, significant asthma-specific VOCs were identified, emphasizing the potential of this remote breath collection method for diagnosing asthma in preschool children.