Olaf Holz - Breath analysis following experimental endotoxin challenge in healthy volunteers
Olaf Holz is a bioengineer, trained at the Hamburg University of Applied Sciences. After working in toxicogenetics in the Department of Occupational and Environmental Health at the University of Hamburg and the Department of Occupational Health at the University of Vienna for 4 years, he changed to respiratory health and worked in the Hospital Grosshansdorf in the research group of Professor Magnussen for 18 years. Here the focus was on research in non-invasive methods to monitor airway inflammation, especially induced sputum and exhaled nitric oxide. He achieved his PhD in environmental Sciences from the University of Lüneburg in 2006. The work on human experimental challenge models (ozone, LPS), and their use in pharmaceutical proof of concept studies continued after changing to the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM in 2010, were he is now a group leader for non-invasive clinical method development in the department of Clinical Airway Research.
It´s still unclear, how airway inflammation effects the breath VOC profile. We therefore analyzed breath volatile organic compounds (VOC) following experimental endotoxin (LPS) challenge of healthy human volunteer subjects.
10 healthy, non-smoking volunteers were recruited for this study. Breath was collected during the following visits: screening (V1), baseline (V2), following overnight fasting in the morning before (V3a), in the late afternoon following a segmental LPS challenge (V3b), and following an overnight fasting period approximately 22 h after the segmental challenge (V4). After a 4 week washout period the subjects underwent a whole lung LPS inhalation challenge. A breath sample was collected about 1 week before (V5), the morning before (V6a) and in the early afternoon (V6b) following the inhalation challenge. Airway inflammation was assessed by bronchoscopy (BAL) after the segmental challenge and using sputum analysis after the inhalation challenge. Patients inhaled room air through a VOC and sterile filter and exhaled into an aluminum reservoir tube. Breath was loaded simultaneously onto 4 Tenax and 2 carbon adsorption tubes and analyzed by GC-MS.
The segmental and the inhalation LPS challenge caused a clear inflammatory response characterized by a massive influx of neutrophils and monocytes into the airways (BAL median (IQR): 3.0(4.2) vs. 64.0(7.3), sputum: 33.9(26.8) vs. 78.3(13.5), respectively). We observed changes in VOC patterns related to food intake during the study days. Among these were terpens, acetone, and ethanol, which increased in the samples taken after the lunch break (V3b and V6b). There were also study procedure related changes in the VOC profile. Propanol-1 and propanol-2, compounds of hand and skin disinfection solutions, increased with the duration of time spend in our institute and were found increased on days when ECG and skin prick test were performed. For a number of aldehydes we observed changes which could be related to the change in airway inflammation.
The longitudinal breath analysis in this study shows that metabolic and environmental processes clearly affect the VOC patterns, therefore an identification of VOCs is strongly recommended as pattern changes detected by eNOSE or other sensor based instruments could be misinterpreted. It’s tempting to speculate that the observed changes in breath aldehyde levels reflect oxidative stress during induced airway inflammation.