Development and comparison of novel non-invasive methods for analyzing airway inflammation

Airway inflammation monitoring, preferably by non-invasive methods, is a crucial step in the safety evaluation of novel drugs. In a research project conducted by the Fraunhofer ITEM Division of Airway Research since February 2017, the respiratory inflammation upon segmental bronchoscopic application of endotoxin (lipopolysaccharide, LPS) is characterized and compared with the inflammation induced by inhalation challenge with LPS. The project is performed in collaboration with the Fraunhofer ITEM Department of Aerosol Technology, the Institute for Radiology of the Hannover Medical School, and the University of Gothenburg.

Outstanding features of this project are the examination of the lung by xenon-enhanced magnetic resonance imaging (MRI) and the comparison of different methods for non-invasive monitoring of the airway inflammation, including analysis of volatile organic compounds in exhaled breath, analysis of exhaled particles, and collection and chemical analysis of induced sputum by means of different biomarkers including chip cytometry. In addition, the biological materials collected during bronchoscopy, such as bronchoalveolar lavage fluid and samples collected by brush and forceps biopsy, as well as serum samples will be used for detailed characterization of the inflammatory response.

The newly developed method of gas-enhanced magnetic resonance imaging with hyperpolarized xenon is opening up the new possibility to analyze and quantify inflammatory processes and impaired lung function and even diffusion and perfusion limitations in a space-resolved manner. By means of a polarizer available at Fraunhofer ITEM, xenon can be hyperpolarized on site for direct use in MRI examinations. For hyperpolarized xenon as a medical device produced in-house, a simplified compliance inspection has been completed, so that this technique is henceforth available also for use in clinical trials with drugs and medical devices.