Medicinal Chemistry & Chemical Biology, Short talk
MC-025

Feasibility of breath exhalomics studies with infants and young children for early detection of cystic fibrosis inflammation and infection

T. Bruderer1,2, A. Baghdasaryan1, J. Wyler2, M. Kohler3, R. Zenobi2*, A. Möller1*
1University Children's Hospital, Division Respiratory Medicine, Zürich, Switzerland, 2Swiss Federal Institute of Technology in Zürich, Department of Chemistry and Applied Biosciences, Zürich, Switzerland, 3University Hospital, Department of Pulmonology, Zürich, Switzerland

Objectives: Early and often subclinical pulmonary infection and pronounced neutrophilic inflammation are major contributors to CF-related morbidity. There is a causal relationship between high airway neutrophil elastase activity and the development of bronchiectasis. Early detection of disease and disease-associated complications is crucial for implementing timely therapeutic measures to reduce disease burden and improve prognosis. Secondary Electrospray Ionisation Mass Spectrometry (SESI-MS) is an extremely efficient method for ionizing compounds in exhaled breath allowing extending the number of compounds that can be detected in exhaled breath.

Methods: We developed a sampling device which can be used with non-cooperative children with tidal breathing and facemask. The device was optimized for real-time, sensitive analysis by introducing a temperature, humidity and flow controlled air supply. A feasibility study was done with 20 children (age range 3-12y), 9 with stable CF and 11 healthy controls. All children performed 6 measurements with tidal breathing and facemask (TBFM) and single breath with mouthpiece (SBMP).

Results: The success rate was 100% for TBFM but SBMP analysis was not feasible for 3 children of age 3y, 4y and 6y. The average m/z features per measurement in positive mode were 713 for SBMP and 702 (-2%, SD11%) for TBFM for molecules detected in the range of m/z = 50 - 320. Data analysis is on-going with a set of 28 breath biomarkers (amino acids, fatty acids and aldehydes) which we identified during previous exhalomics studies with adults. Non-targeted screening for statistical significantly different features (between groups) has started and will be followed by compound identification based on high-performance liquid chromatography (UHPLC-HRMS/MS) of exhaled breath condensates and pure reference standards. Our preliminary results reveal comparable number of features and intensities between TBFM and SBMP.

Conclusions: Breath exhalomics studies with SESI-MS are feasible in children from 3 years of age. Measurements by TBFM and SBMP resulted in similar number of features and intensities. Therefore, optimized SESI-MS can be applied in young non-cooperative children.