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

Asthma is the most common chronic respiratory disease in children.However, distinguishing asthma from other respiratory complaints in preschool age remains a diagnostic challenge.Secondary electrospray ionization high resolution mass spectrometry (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.