Volatile organic compound breath signatures of children with cystic fibrosis by real-time SESI-HRMS

Abstract

Early pulmonary infection and inflammation result in irreversible lung damage and are major contributors to cystic fibrosis (CF)-related morbidity. An easy to apply and noninvasive assessment for the timely detection of disease-associated complications would be of high value. We aimed to detect volatile organic compound (VOC) breath signatures of children with CF by real-time secondary electrospray ionisation high-resolution mass spectrometry (SESI-HRMS).A total of 101 children, aged 4–18 years (CF=52; healthy controls=49) and comparable for sex, body mass index and lung function were included in this prospective cross-sectional study. Exhaled air was analysed by a SESI-source linked to a high-resolution time-of-flight mass spectrometer. Mass spectra ranging from m/z 50 to 500 were recorded.Out of 3468 m/z features, 171 were significantly different in children with CF (false discovery rate adjusted p-value of 0.05). The predictive ability (CF versus healthy) was assessed by using a support-vector machine classifier and showed an average accuracy (repeated cross-validation) of 72.1% (sensitivity of 77.2% and specificity of 67.7%).This is the first study to assess entire breath profiles of children with SESI-HRMS and to extract sets of VOCs that are associated with CF. We have detected a large set of exhaled molecules that are potentially related to CF, indicating that the molecular breath of children with CF is diverse and informative.

Optimizing Secondary Electrospray Ionization High-Resolution Mass Spectrometry (SESI-HRMS) for the Analysis of Volatile Fatty Acids from Gut Microbiome

“…Different temperatures of the sample inlet (80‒160 °C) have been adopted in previous researches using SESI-MS [ 5 , 30 , 34 , 36 , 37 ]. Similarly, a recent study by Weber et al analyzed breath VOC profiles of children with cystic fibrosis by setting a sampling line at 130 °C [ 8 ].…”

“…Over the past two decades, the mass spectrometry-based methodologies such as proton-transfer-reaction mass spectrometry (PTR-MS) and selected ion flow tube mass spectrometry (SIFT-MS), in addition to the gold-standard gas chromatography-mass spectrometry (GC-MS), have been used for the detection and analysis of gas-phase volatile organic compounds (VOCs) [ 1 , 2 , 3 , 4 ]. In recent years, secondary electrospray ionization mass spectrometry (SESI-MS) has also emerged for the studies of gas-phase VOCs from yeast, plant, bacteria, and breath [ 5 , 6 , 7 , 8 ]. SESI-MS is a real-time, non-invasive, and sensitive technique with a reported limit of detection at as low as 0.2 parts per trillion by volume (ppt) [ 9 ].…”

Breath-Taking Perspectives and Preliminary Data toward Early Detection of Chronic Liver Diseases

“…), who described fetor hepaticus , the musty breath of subjects undergoing liver failure [ 40 ]. The last five decades have seen the evolution of more quantitative and accurate instruments that led to the discovery of a considerable number of breath compounds associated with several diseases [ 41 , 42 , 43 ], including Alzheimer’s [ 44 , 45 ], Parkinson’s [ 44 ], schizophrenia [ 46 , 47 ], multiple sclerosis [ 48 , 49 ], breast cancer [ 50 , 51 ], colorectal cancer [ 51 , 52 , 53 ], lung cancer [ 51 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ], asthma [ 61 , 62 , 63 , 64 , 65 ], chronic obstructive pulmonary disease (COPD) [ 61 , 66 , 67 , 68 , 69 , 70 , 71 ], cystic fibrosis [ 72 , 73 , 74 , 75 , 76 ], and COVID-19 [ 77 , 78 ].…”

Detection of Volatile Organic Compounds with Secondary Electrospray Ionization and Proton Transfer Reaction High-Resolution Mass Spectrometry: A Feature Comparison

“…Both instruments are comparable in terms of mass resolving power (Table 1) and reported sensitivity (down to the ppt level [7,9]. For PTR, the ionization mechanism is precisely known, which allows the calculation of gas-phase concentrations for the volatiles of interest [10].…”