Inflammatory Markers in Sputum After LPS Inhalation

The Role of Inhaled Particle Size on the Inflammatory Response Induced by Endotoxin Inhalation

The purpose of the study is to measure inflammatory biomarkers in sputum and peripheral blood in healthy volunteers after inhalation of single doses of LPS (20 mcg) administered as particles of different sizes.

Endotoxins are inflammatory substances present in the environment. In man, the inhalation of the lipopolysaccharride moiety (LPS) induces measurable immune responses. With an inhaled single dose of 20 micron, the inflammatory response in man is sub-clinical. During bronchoprovocation tests with allergens, the particle size determines to a large extent the intensity of the response. the response to LPS as a function of particle size is not known and will be studied in this study.

Inclusion Criteria:

• healthy volunteer, non-smoking or ex-smoker >1mth and <10packs/year
• normal ECG
• normal lab values for hematology, ionogram, AST, ALT, alk phosphatases, urea, creatinine and CRP
• FEV1/forced vital capacity >0.7 and FEV1>80% of predicted value
• able to produce valid sputum following induction (>=50% viable cells, <50% squamous cells and <60% neutrophils)
• females must be using contraception
• written informed consent

Exclusion Criteria:

• infection within 14 days
• history of bronchial asthma
• obstructive respiratory condition with FEV1 <70% of theoretical value