Breath-taking Discoveries : Unveiling the Diagnostic Potential of Exhaled Breath Analysis in Clinical Settings

Breath analysis offers tremendous potential for biomarker-based diagnostic approaches, since it allows for easy and non-invasive sample collection. The objective of this thesis was to explore exhaled breath as an alternative biofluid in clinical settings. Therefore, three clinical studies were conducted. Two non-targeted metabolomics studies elucidated the non-volatile breathome using high-resolution FT‑ICR-MS combined with various biostatistical analyses. A third study, conducted during the COVID-19 pandemic, focused on detecting SARS-CoV-2 RNA in exhaled breath utilising qRT-PCR methods. The first metabolomics study examined breath samples initially characterising the non-volatile breathome of healthy individuals by identifying >2500 metabolites. Furthermore, the previously developed approach was applied in a subsequent study to explore the breathome of Parkinson’s disease (PD) patients. The non-volatile breathome of PD patients, firstly described in this work, exhibits significant differences compared to that of healthy individuals. These breakthrough discoveries present potential biomarker candidates for PD. The third study examined exhaled breath for detecting SARS‑CoV‑2. Remarkably, this investigation depicts the first time-dependent progression of viral loads in exhaled breath during a SARS-CoV-2 infection. The results revealed that infected patients shed up to >1 million virus copies per hour into the environment via regular breathing. Noteworthy, the viral load in breath samples did not correlate with the corresponding swab samples, suggesting exhaled breath to be a more suitable biofluid for assessing individual infectivity and identifying superspreaders. These studies highlight the extraordinary potential of exhaled breath and lay the foundation for further investigations of the non-volatile breath profile, paving the way for discovering biomarkers.