pulmonary inflammation and activation of coagulation
Conditions
Interventions
Subjects will receive saline in one lungsegment and in the other lung they will
be challenged with also saline (placebo, n=8), saline with 10 *g carbon
nanoparticles (n=4), saline with 50 *g carbon
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Healthy male subjects between 18 and 45 years of age * No clinically significant findings during physical examination and haematological and biochemical screening. * Baseline FEV1 > than 80% of predicted value. * No current smoking for at least 1 year and less than 5 pack years of smoking history
Exclusion criteria
Exclusion criteria: * History of any relevant disease * A history of smoking within the last 12 months, or regular consumption of greater than three units of alcohol per day * Administration of any investigational drug within 30 days of study initiation * Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation * History of serious drug-related reactions, including hypersensitivity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Neutrophil, eosinophil and mast cell responses in blood and bronchoalveolar lavage fluid (BALF): * Total leukocyte counts and differentials * Neutrophil response (LTB4, myeloperoxidase (MPO)) * Eosinophil response (eosinophil cationic protein (ECP)) * Mast cell response (chymase, tryptase) Activation of cytokine- and chemokine network : * Proinflammatory cytokines: TNF-*, IL-5, IL-6, IL-17, VEGF, c-kit ligand, * Anti-inflammatory cytokines : IL-10 * CXC chemokines: IL-8, GRO-*, IP-10 * CC chemokines: MCP-1, MIP-1*, MIP-1* General: C-reactive protein measurement | — |
Secondary
| Measure | Time frame |
|---|---|
| Activation of coagulation and fibrinolysis (BALF and/or blood): * Coagulation: TAT complexes, F1+2 prothrombin fragment, soluble tissue factor, D-dimers * Fibrinolysis: PA activity, tPA, PAI-1, PAP complexes * Anticoagulant proteins: protein C, activated protein C, antithrombin, soluble thrombomodulin Amino acid pattern in exhaled breath condensate Metabolomic fingerprint as obtained by Liquid chromatography-mass spectrometry (LC-MS) Lung functions will be assessed before and after the provocations. | — |
Countries
Netherlands
Outcome results
None listed