This pilot study is planned to assess the suitability of a low dose Lipopolysaccharide (LPS) inhalation as a challenge model. As LPS effects are based on a different mode of action, this challenge model will provide the possibility to test a wider spectrum of potential drugs in the future. Provided that the LPS response is reproducible, it is planned to test whether a single high dose of inhaled steroid can serve as a positive control in the LPS model. Another major aim of the study is to test a variety of novel tools for the non-invasive assessment of airway inflammation induced by LPS challenge.
In this study, airway inflammation will be induced by LPS inhalation. In case a neutrophilic airway inflammation can be safely induced by inhaled LPS, the LPS challenge will be repeated. If neutrophil airway inflammation after LPS challenge is reproducible LPS challenge will be repeated after pre-treatment with a single high dose of inhaled fluticasone propionate. To determine airway inflammation, the subjects' exhaled breath will be analyzed by different techniques, and blood samples as well as induced sputum will be collected.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
20,000 EU of Clinical Center Reference Endotoxine (CCRE) will be applied by an AKITA® Jet Nebulizer under the constant supervision of the site staff.
The dosage of FP will be 2 mg. This dosage will be inhaled by 4 puffs of Flutide® forte 500 Diskus® 500 µg / dose according to the package insert.
Fraunhofer ITEM
Hanover, Lower Saxony, Germany
Induced sputum
• neutrophil cell count
Time frame: 6 h after the start of LPS challenge
lung function
Change of lung function directly at the end of each challenge as well as up to 24 h after the end of exposure compared with baseline
Time frame: at the end of each LPS challenge and up to 24 hours
Blood samples
Differential cell count
Time frame: before and 6 h after the start of LPS challenge
Exhaled breath
Pre-concentrated samples (30 L, 10-15 exhalations) on a specific substrate for later analysis by Gas Chromatorgraphy - Mass Spectrometry (GC-MS) or Smart-Nose and exhaled breath temperature
Time frame: 3 hours after the start of LPS challenge
Induced sputum
soluble biomarkers such as but not limited to Myeloperioxidase (MPO), Surfactant Protein D (SP-D), Interleukin (IL-8)
Time frame: 6 h after the start of LPS challenge
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